Knee Injection Side Effects: What to Expect and When to Call Your Doctor

Key Takeaways

Most knee injection side effects are mild and resolve within 24-48 hours
Common reactions include soreness, mild swelling, and temporary warmth at the injection site
Gel injections and cortisone have different side effect profiles, with cortisone posing long-term cartilage risks
Warning signs like fever, severe swelling, or worsening pain need prompt medical attention
Following aftercare instructions significantly reduces your risk of complications

If you’re considering a knee injection for arthritis pain, questions about side effects are natural. What will it feel like afterward? How long will any discomfort last? And what symptoms should prompt a call to your doctor?

The good news: knee injections are generally safe, with serious side effects being rare. Most people experience only mild, temporary reactions that resolve on their own. This guide walks you through what to expect, how gel injections differ from cortisone, and the specific warning signs that need medical attention.

Understanding Injection Side Effects

When any medication is injected into your knee joint, your body responds to both the procedure and the substance itself. This is normal. Understanding what’s happening helps you distinguish between expected reactions and genuine concerns.

Why Side Effects Occur

Physical trauma: A needle entering your joint causes minor tissue irritation

Volume effect: Adding fluid to the joint creates temporary pressure

Inflammatory response: Your immune system reacts to foreign substances

Medication effects: The injected substance has its own properties

Setting Realistic Expectations

Most patients tolerate knee injections well. Studies show that approximately 5-10% of patients experience noticeable side effects, and the vast majority are mild and short-lived. Serious complications occur in less than 1% of procedures.

Knowing what’s normal helps you avoid unnecessary worry while staying alert to symptoms that genuinely need attention.

Common Side Effects (Occur in 5-10% of Patients)

These reactions are your body’s normal response to the injection procedure. They typically resolve within a few days without treatment.

Injection Site Soreness

The most frequently reported side effect is tenderness where the needle entered your skin and joint.

What’s Normal:

Mild to moderate ache or tenderness for 24-48 hours
Discomfort when touching the injection area
Temporary increased stiffness
Pain that gradually improves each day

What Helps:

Apply ice for 15-20 minutes, 3-4 times daily for the first 24 hours
Take acetaminophen (Tylenol) if needed
Rest the joint but maintain gentle movement
Avoid strenuous activity for 24-48 hours

Mild Swelling

Some puffiness around your knee is common, especially in the first day or two after injection.

What to expect:

Slight fullness or tightness in the joint
Swelling that peaks within 24 hours
Gradual decrease over 2-3 days

The swelling occurs partly from the injected fluid and partly from your body’s inflammatory response. It’s not a sign that something went wrong.

Warmth or Redness

Your knee may feel slightly warm to the touch or appear mildly red around the injection site. This is a normal part of the healing process.

Key distinction: Normal warmth is mild, stays localized, and improves over time. Warmth that increases, spreads, or is accompanied by fever requires medical evaluation.

Temporary Increased Pain (Pseudoseptic Reaction)

Sometimes called a “post-injection flare,” this occurs when pain temporarily worsens before improving. It can be alarming but is usually harmless.

Understanding Post-Injection Flares

With cortisone injections: Flares occur in 5-10% of patients when steroid crystals temporarily irritate the joint lining. Pain may be significant but typically peaks within 24-48 hours and resolves by day 3.

With gel injections: Flares are less common (about 2-3% of patients) because hyaluronic acid is a natural substance similar to your joint fluid.

How to tell it’s a flare, not infection:

Starts within 24-48 hours of injection
No fever or chills
Improves by day 3
Doesn’t get progressively worse

Gel Injection vs. Cortisone: Side Effect Comparison

While both types of knee injections can cause the common side effects described above, they have important differences in their safety profiles.

Side Effect	Gel Injections (HA)	Cortisone
Injection site soreness	Common (24-48 hrs)	Common (24-48 hrs)
Mild swelling	Common	Common
Post-injection flare	Rare (2-3%)	More common (5-10%)
Blood sugar elevation	None	Yes (concern for diabetics)
Facial flushing	Rare	More common, especially in women
Cartilage damage risk	None documented	Yes, with repeated use
Frequency limits	Every 6 months	3-4 times per year maximum
Long-term joint effects	Neutral to protective	May accelerate arthritis

The Key Difference: Long-Term Cartilage Effects

This is the most important distinction between gel injections and cortisone.

Gel Injections: No Cartilage Damage Risk

Hyaluronic acid (HA) gel injections work by supplementing your joint’s natural lubricating fluid. Research shows they do not damage cartilage and may even have protective effects. You can receive gel injections every six months without concerns about accelerating arthritis progression.

Cortisone: Cartilage Concerns with Repeated Use

Research shows that repeated cortisone injections can accelerate cartilage breakdown. A 2019 study in JAMA found that patients receiving multiple cortisone injections had a 57% higher risk of eventually needing knee replacement compared to those receiving hyaluronic acid. This doesn’t mean occasional cortisone use is harmful, but frequent injections (more than 3-4 per year) carry real risks.

For a detailed comparison, see our guide: HA vs. Cortisone: Which Is Right for You?

Rare but Serious Side Effects

While uncommon, certain side effects require prompt medical attention. Knowing these warning signs helps you get timely care if needed.

Signs of Infection

Joint infection (septic arthritis) is the most serious potential complication. It occurs in fewer than 1 in 1,000 injections when proper sterile technique is used, but requires immediate treatment if it occurs.

Call Your Doctor Immediately If You Have:

Fever above 100.4F (38C)

Severe pain that worsens rather than improves after 48 hours

Increasing redness that spreads beyond the injection site

Hot, swollen knee that continues to worsen

Chills or feeling generally unwell

Drainage or pus from the injection site

Infection symptoms typically appear 2-7 days after injection. Early treatment with antibiotics is highly effective, which is why prompt medical attention matters.

Allergic Reactions

True allergic reactions to knee injections are uncommon but can occur, particularly with certain gel injection brands derived from rooster combs (avian-derived products).

Mild allergic symptoms:

Itching or hives near the injection site
Mild rash
Localized swelling beyond the joint

Severe allergic symptoms (seek emergency care):

Difficulty breathing or swallowing
Swelling of face, lips, or tongue
Widespread hives
Dizziness or rapid heartbeat

If you have allergies to birds, chicken, eggs, or feathers, inform your doctor before receiving gel injections. Non-avian alternatives (like Euflexxa or Durolane) are available and equally effective.

Who Has Higher Risk of Side Effects?

Certain individuals may be more likely to experience side effects or need special precautions.

Allergies (Avian-Derived Products)

Bird or egg allergies: Some gel injection brands (Synvisc, Monovisc, Gel-One) are derived from rooster combs and contain trace avian proteins. If you have poultry allergies, request a non-avian brand.

Autoimmune Conditions

Rheumatoid arthritis, lupus, or other autoimmune conditions: Your immune system may react differently to injected substances. Discuss your condition with your provider and watch for unusual reactions.

Diabetes

Cortisone and blood sugar: Steroid injections can significantly raise blood glucose levels for 3-7 days. This effect does NOT occur with gel injections. Diabetics should monitor blood sugar more frequently after cortisone and may need to adjust medication.

Blood Thinners

Anticoagulant medications: Patients on warfarin, Eliquis, Xarelto, or similar blood thinners may experience more bruising at the injection site. The injection is usually still safe, but discuss with your doctor.

How to Minimize Side Effects

Following proper aftercare significantly reduces your risk of complications and discomfort.

Immediately After Your Injection

First 24-48 Hours

Apply ice: 15-20 minutes, 3-4 times daily to reduce swelling

Rest the joint: Avoid strenuous activity, heavy lifting, or prolonged standing

Keep the site clean: Avoid swimming, hot tubs, or baths for 24 hours

Stay mobile: Gentle walking is fine and helps distribute the medication

Use acetaminophen if needed: Tylenol is preferred over NSAIDs, which may reduce injection effectiveness

Days 2-7

Gradually resume normal activities as tolerated
Continue icing if swelling persists
Watch for warning signs (fever, worsening pain, spreading redness)
Most side effects should resolve by day 3-4

When to Call Your Doctor: Specific Warning Signs

Use this checklist to determine when professional evaluation is needed.

Call Your Doctor’s Office If:

Pain doesn’t improve after 48 hours
Swelling increases rather than decreases
You develop a low-grade fever (99-100.4F)
The injection site becomes increasingly red or warm
You have numbness or tingling that persists

Seek Emergency Care If:

Fever above 101F with joint pain
Severe pain and swelling that came on suddenly
Difficulty breathing or swallowing (possible allergic reaction)
Facial swelling or widespread hives
You cannot bear any weight on the joint

When in Doubt, Call

It’s always better to check with your provider and be reassured than to wait and worry. Most offices have a nurse line for after-hours questions. Don’t feel embarrassed about calling, this is exactly what medical support is for.

Long-Term Safety Considerations

Gel Injections: Excellent Long-Term Safety

Hyaluronic acid injections have been used for over 25 years with an excellent safety record. They do not accumulate in your body, do not damage cartilage, and can be repeated every six months as needed. Research shows no increase in joint replacement risk with gel injections.

Learn more: Hyaluronic Acid Injections: Complete Treatment Guide

Cortisone: Moderation Is Key

Cortisone remains valuable for acute flares and occasional use. The concern is with frequent, repeated injections. To protect your joint health:

Limit to 3-4 cortisone injections per year per joint
Wait at least 3 months between injections
Consider alternating with gel injections
Use cortisone for acute inflammation, not routine maintenance

Frequently Asked Questions

How long do side effects from knee injections last?

Most common side effects (soreness, mild swelling, stiffness) resolve within 2-3 days. If symptoms persist beyond 5-7 days or worsen after the first 48 hours, contact your provider.

Is it normal to feel worse before feeling better?

Yes, especially with cortisone. A “post-injection flare” can temporarily increase pain for 24-48 hours before relief begins. This occurs in 5-10% of cortisone patients and 2-3% of gel injection patients.

Can I drive myself home after a knee injection?

Most people can drive after a knee injection. However, if you receive sedation or feel unsteady after the procedure, arrange for a ride. Your knee may feel stiff or numb initially from local anesthetic.

When can I exercise after a knee injection?

Avoid strenuous exercise for 24-48 hours after injection. Gentle walking and range-of-motion movements are fine and even encouraged. After 2-3 days, you can typically resume normal activities as tolerated.

Do side effects get worse with repeated injections?

Not typically for gel injections, which maintain consistent safety profiles. With cortisone, some patients report diminishing benefits over time, but side effects don’t necessarily increase. The main concern with repeated cortisone is cumulative cartilage effects.

What if I think I’m having an allergic reaction?

For mild symptoms (localized itching, minor rash), call your doctor’s office for guidance. For severe symptoms (difficulty breathing, facial swelling, widespread hives), call 911 or go to the emergency room immediately.

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Last medically reviewed: January 2026

Medical Disclaimer: This article is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider about questions specific to your condition and treatment. If you experience concerning symptoms after a knee injection, contact your provider or seek emergency care as appropriate.