Cephalexin vs Amoxicillin: Key Differences and What You Need to Know

When you’re prescribed an antibiotic, it’s easy to assume they’re all the same. But cephalexin, a first-generation cephalosporin antibiotic used to treat skin, bone, and respiratory infections and amoxicillin, a penicillin-class antibiotic commonly used for ear, sinus, and urinary tract infections work differently, even if they both fight bacteria. They’re not interchangeable, and choosing one over the other depends on your infection type, medical history, and even whether you’re allergic to penicillin.

Amoxicillin is one of the most common antibiotics in the world, often the first choice for strep throat, pneumonia, or ear infections. But if you’ve ever been told you can’t take penicillin because of an allergy, cephalexin, a structurally different antibiotic in the cephalosporin family becomes your go-to alternative. About 10% of people with penicillin allergies react to cephalosporins like cephalexin, so it’s not always safe—but for most, it’s a solid backup. Cephalexin also lasts longer in your body, so you might take it fewer times a day compared to amoxicillin, which often needs three or four doses daily.

Side effects are similar—nausea, diarrhea, upset stomach—but some people report less digestive trouble with cephalexin. Amoxicillin can sometimes cause a rash, especially in kids with mono, which isn’t always an allergy. Cephalexin doesn’t have that same trigger. If you’ve had trouble with one, switching to the other might help. Both are available as generics, so cost isn’t usually a deciding factor. What matters is which one matches your infection and your body’s history.

You won’t find one antibiotic that works for every bug. Some infections respond better to amoxicillin because it covers a wider range of common bacteria, especially those causing respiratory or urinary issues. Cephalexin shines in skin and soft tissue infections, like cellulitis or abscesses, where it penetrates tissue more effectively. If you’ve had a recurring skin infection, your doctor might lean toward cephalexin. If it’s a persistent ear infection, amoxicillin is still the standard.

And here’s something most people don’t realize: antibiotics don’t work the same for everyone. Your age, kidney function, or even what you ate before taking the pill can change how well it works. That’s why you can’t just grab the same one your friend used last time. What worked for them might not work for you—or could even cause harm.

Below, you’ll find real comparisons, patient experiences, and medical insights that break down exactly when to use cephalexin versus amoxicillin, what side effects to watch for, and how to know if your treatment is working—or if you need to switch.