Background The aim of the present study was to assess the effectiveness of 4 different remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS). Methods: The participants in the four RIPC groups received different RIPC treatments in the arms at a low altitude; the control group did not receive a specific sham treatment. The participants were then flown to a High Altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. We performed an intention-to-treat analysis. Results: A total of 250 participants were included with 50 participants in each group. The total AMS incidence in all participants was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, whereas 15 AMS cases (30%) occurred both in the RIPC A and RIPC B groups (relative risk 1.3; 95% confidence interval 0.8 - 2.3; chi 2 = 1.099; p = 0.29), and 8 AMS cases (16%) occurred both in the RIPC C and D groups (RR 2.5; 95% CI 1.2 - 5.2; chi 2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p <0.001). Conclusion: This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to the results of this study. Methods The participants in the four RIPC groups received different RIPC treatments in the arms at a low altitude; the control group did not receive a specific sham treatment. The participants were then flown to a High Altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. We performed an intention-to-treat analysis. Results A total of 250 participants were included with 50 participants in each group. The total AMS incidence in all participants was 26.4%. A total of 20 AMS cases (40%) occurred in the control group after arrival at high altitude, whereas 15 AMS cases (30%) occurred both in the RIPC A and RIPC B groups (relative risk 1.3; 95% confidence interval 0.8 - 2.3; chi(2 )= 1.099; p = 0.29), and 8 AMS cases (16%) occurred both in the RIPC C and D groups (RR 2.5; 95% CI 1.2 - 5.2; chi(2 )= 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p <0.001). Conclusion This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to the results of this study.