Tetracycline vs Doxycycline: Key Differences and When to Use Each

When you need an antibiotic for acne, Lyme disease, or a respiratory infection, you might hear your doctor mention tetracycline, a broad-spectrum antibiotic first introduced in the 1940s that works by stopping bacteria from making proteins. Also known as old-school tetracycline antibiotics, it’s still used—but less often than its newer cousin. doxycycline, a modified version of tetracycline with better absorption and longer action in the body. It’s one of the most commonly prescribed antibiotics today for everything from tick bites to urinary tract infections. Both belong to the tetracycline class, but that’s where the similarity ends.

Here’s the real difference: doxycycline works better in your body. It’s absorbed more completely from your gut, stays active longer, and doesn’t get tied up by dairy or antacids as much as tetracycline does. If you take tetracycline with milk, yogurt, or calcium supplements, it barely works—doxycycline? You’re fine. Dosing is simpler too. Tetracycline usually needs to be taken four times a day on an empty stomach. Doxycycline? Often just once or twice daily, and you can take it with food if your stomach gets upset. That’s why most doctors pick doxycycline now—it’s easier to stick with.

Side effects are similar but not equal. Both can cause nausea, sun sensitivity, or yeast infections. But tetracycline is more likely to wreck your stomach lining if taken on an empty stomach. Doxycycline is less harsh on the gut but can still make you burn easily in the sun. And here’s something most people don’t know: tetracycline can permanently stain kids’ teeth if used before age 8. Doxycycline is safer for younger patients in low doses, though doctors still avoid it in kids under 12 unless absolutely necessary.

They’re both used for similar infections—acne, chlamydia, Rocky Mountain spotted fever, some types of pneumonia—but doxycycline is the go-to for tick-borne illnesses. It’s the first-line drug for Lyme disease. Tetracycline? Rarely used for that anymore. For acne, doxycycline is preferred because it penetrates skin better and lasts longer. If you’re allergic to penicillin, either could be an option—but doxycycline is more reliable.

Cost matters too. Tetracycline is usually cheaper because it’s been around for decades. But if you’re paying out of pocket, the real cost isn’t just the pill price—it’s how many times you have to take it, whether you need to plan meals around it, or if you end up with a bad reaction because you took it with coffee or antacids. Doxycycline might cost a bit more per pill, but you take less of it, and it works better. That’s why it’s the default choice in most clinics.

There’s no one-size-fits-all answer. If you’ve been on tetracycline for years and it’s working, don’t switch unless your doctor says so. But if you’re starting a new course, or your old antibiotic didn’t work, doxycycline is almost always the better bet. It’s not magic—it won’t fix everything—but when it comes to choosing between these two, the science and real-world use point clearly to one winner.

Below, you’ll find real comparisons, patient experiences, and expert breakdowns on how these two antibiotics stack up against each other—and what alternatives might work even better depending on your condition.