RATIONALE: The relationship between cigarette smoking and acute mountain sickness (AMS) is not clear. OBJECTIVE: To assess AMS risk and altitude acclimatisation in relation to smoking. METHODS: 200 healthy non-smokers and 182 cigarette smokers were recruited from Han lowland workers. These were men without prior altitude exposure, matched for age, health status and occupation, who were transported to an altitude of 4525 masl. MEASUREMENTS: AMS, smoking habits, arterial saturation (SpO2), haemoglobin (Hb), lung function and mean pulmonary artery pressure (PAPm) were assessed upon arrival and after 3 and 6 months. MAIN RESULTS: Compared with non-smokers, smokers had a lower incidence of AMS and lower AMS scores than non-smokers upon arrival; higher Hb and PAPm associated with lower SpO2 at 3 and 6 months at altitude; and lower forced expiratory volume in 1 s and maximal voluntary ventilation at 3 and 6 months. CONCLUSIONS: Smoking slightly decreases the risk of AMS but impairs long-term altitude acclimatisation and lung function during a prolonged stay at high altitude.