BACKGROUND: Acute mountain sickness (AMS) may occur after rapid ascents to altitudes >2500 m. Cusco (3350 m) in Peru is a popular destination for altitude inexperienced travellers. This study aimed at evaluating the incidence and risk factors for AMS among a cohort of foreign Spanish language students in Cusco. METHODS: We performed a cohort study among young healthy foreign Spanish language students arriving to Cusco between 2012 and 2016. Consenting students answered an enrollment questionnaire on demographics, travel history and intended AMS preventive behaviour within 48 h of arrival. At 4-5 days after enrollment participants answered a second questionnaire about actual preventive behaviour before symptoms and the development of symptoms compatible with AMS during their first 48 h in Cusco. We used the 2018 Lake Louise Scoring System for AMS diagnosis. Participants with headache and a score ≥ 3 were considered to have AMS. RESULTS: We enrolled 142 language students, the median age was 21 years (interquartile range 20-25) and 57% were female. Participants decreased physical activity (38%), increased fluid intake (34%), drank coca leaf tea (34%), took acetazolamide (16%) and acclimatized at a lower altitude (6%) to prevent AMS. Thirty-nine percent had AMS. In the multivariate analysis, obesity [odds ratio (OR) 14.45 (2.33-89.6)] and female sex [OR 4.32 (1.81-10.28)] were associated with increased risk of AMS. Taking acetazolamide [OR 0.13 (0.03-0.56)] was associated with decreased AMS risk. Consumption of coca leaf tea was not associated with decreased risk of AMS. CONCLUSIONS: In our cohort, AMS affected two out of five travellers. Obesity and female sex were associated with increased risk. Drinking coca leaf tea for prevention did not decrease the risk of AMS. Acetazolamide prophylaxis was associated with decreased risk of AMS.