Acetazolamide roughly halves the risk of altitude sickness. The evidence is real.

Acetazolamide, the drug most commonly recommended to prevent altitude sickness, works — a Cochrane systematic review of 64 trials found it reduced the risk of acute mountain sickness by roughly half [s1]. That is an unusually clear answer for a question travellers ask constantly, and it separates acetazolamide from the herbal preparations sold alongside it, none of which carry comparable evidence. It is also a prescription drug with side effects, which is why the decision to use it belongs in a pre-travel clinic conversation and not in this article.

What altitude illness is

High altitude illness is the umbrella term for the syndromes that can strike above about 2,500 metres, as the air thins and the body struggles to take in enough oxygen [s1]. The mildest and commonest is acute mountain sickness (AMS) — headache, nausea, fatigue, poor sleep — but the spectrum extends to two life-threatening forms: high altitude cerebral oedema (HACE), swelling of the brain, and high altitude pulmonary oedema (HAPE), fluid in the lungs [s1]. Prevention matters because the dangerous forms grow out of an environment, not an infection, and ascending faster than the body can acclimatise is the core risk.

What the prevention review found

The Cochrane review pooled 64 studies and 4,547 participants, most conducted on real mountains and the rest in low-pressure chambers simulating altitude [s1]. In the trials, the drug was generally started ahead of the climb: 24 trials gave it three to five days before ascent, and 23 gave it one to two days beforehand [s1].

For acetazolamide against placebo, drawing on 28 parallel trials, the risk of AMS was reduced with a relative risk of 0.47 (95% confidence interval 0.39 to 0.56), from 16 studies and 2,301 participants, which the reviewers rated moderate-quality evidence [s1]. A relative risk of 0.47 means the drug cut the AMS rate to roughly half of the placebo rate. That is the number behind every guideline that recommends it.

Two other drugs appeared in the comparison. Inhaled budesonide reduced AMS with a relative risk of 0.37 (95% CI 0.23 to 0.61), but from only two small trials totalling 132 participants, rated low-quality [s1]. Dexamethasone, a steroid, did not show a clear benefit: relative risk 0.60, but with a confidence interval of 0.36 to 1.00 that touches the line of no effect, from four trials and 176 participants, also low-quality [s1]. The evidence base thins quickly once you step away from acetazolamide.

The cost side of acetazolamide

The same review recorded the drug's characteristic nuisance effect. Acetazolamide increased the risk of paraesthesia — the pins-and-needles tingling in fingers and toes that many users report — with a relative risk of 5.53 (95% CI 2.81 to 10.88) [s1]. That is a large increase in a non-dangerous but noticeable side effect, and it is one reason the drug is a considered clinical choice rather than a default. No HAPE events and only a single HACE event were reported in the acetazolamide trials, so the review could not say much about the drug's effect on the severe syndromes — its evidence is about preventing the common, milder AMS [s1].

What the evidence says about treating it once it starts

A separate Cochrane review looked at treating altitude illness that has already begun, and it is a thinner literature: 13 studies enrolling 468 participants, mostly in the European Alps, with follow-up usually under a day [s2]. It did not find high-quality evidence establishing that any single treatment reliably produced complete relief of AMS symptoms in a trial setting [s2]. This matters for expectation-setting: the established response to serious altitude illness is not a pill but descent and oxygen, and the drug evidence is strongest for prevention, weakest for cure.

What this leaves a traveller

The honest summary is that acetazolamide is one of travel medicine's better-supported drugs for a specific job — lowering the odds of acute mountain sickness on a planned ascent — with a moderate-quality evidence base and a well-characterised, mostly benign side effect. It is not a substitute for sensible ascent profiles, and it is not something to source without medical input, because the dose, the timing, and the fit with a person's other conditions and medications are clinical questions. Anyone planning travel to high altitude, particularly with a prior history of altitude illness, has a concrete reason to raise acetazolamide with a travel clinic — and that is where the specifics belong.