A randomized, double-blind, placebo-controlled trial was conducted to investigate the efficacy of prophylaxis by administering compound Danshen dripping pills (CDDPs) on acute mountain sickness (AMS). To this end, a total number of 58 healthy low-altitude inhabitants residing in Beijing were randomized to two treatment sequences, receiving either 270mg CDDPs or placebo during an 11-day trip in Tibet, China, at an altitude of more than 3000 m. The Lake Louise Scoring System (LLSS) was also utilized to access AMS incidence and severity, twice a day, during the research period. AMS was further diagnosed when headaches and LLSS≥ 3 were present. A total of 54 subjects completed the study and no significant difference was observed in the number of individuals with AMS between the groups. However, during the whole observation period, the LLSS values for comprehensive AMS symptoms in the group receiving CDDPs indicated lower occurrence than those in the placebo (CON) group. It is noteworthy that, on day 3 (arrival at Lhasa, altitude 3658 m), AMS symptoms (LLSS=3.79) in the CON group had clearly aggravated (P=0.0475) in contrast to those in the group with administration of CDDPs (LLSS=2.31). Besides, arterial oxygen saturation (SaO2) value for those taking CDDPs was significantly higher than that in the CON group (87.86% vs. 85.72%, P=0.0388) on day 10. These preliminary findings suggested that CDDPs might be regarded as an effective prophylaxis for AMS to a certain extent without any specific adverse effects, relieving clinical manifestations of AMS, especially after rapid ascents (Clinical Trial Registry Number: NCT03270787).