Abstract: Objective To explore the effectiveness of trimetazidine in preventing acute mountain sickness (AMS). Methods Seventy-nine healthy men aged 18-35 years were recruited from the staff of the first medical center of Chinese PLA General Hospital from January to April in 2016. After the collection of baseline data, volunteers were randomly assigned to trimetazidine group (receiving 20 mg of trimetazidine 3 times daily) or placebo group (placebo 3 times daily). After 6 days of intervention, the subjects were taken to an elevation of 4 000 m within 40 hours. The incidence of AMS was evaluated using the revised Lake Louise questionnaire score. Treadmill exercise testing was performed to evaluate exercise tolerance. Pulse oximetry readings were taken before and after the test. Results The incidence of AMS was significantly lower in the trimetazidine group than in the placebo group (30.6% vs 54.3%; P=0.043; OR, 0.37; 95% CI, 0.14-0.98). Among the four symptoms of AMS, the incidence of weakness was lower in the trimetazidine group than in the placebo group (38.9% vs 65.7%; P=0.024; OR, 0.33; 95% CI, 0.13-0.87). Among the volunteers whose oxygen desaturation was more than 10%, the METs value was significantly higher in the trimetazidine group than in the placebo group 9.9 (8.9, 10.0) vs 7.6 (7.1, 9.2), P=0.039. Conclusion Trimetazidine is found to be effective in reducing the incidence of AMS and increasing exercise tolerance after altitude exposure.