Several hypnotic agents commonly recommended for improving sleep at sea level are discouraged at high altitude. We aimed to evaluate the efficacy and safety of drugs prescribed for improving sleep quality in patients with acute exposure to high altitudes by conducting a systematic review and meta-analysis. An electronic search was executed for randomized controlled trials comparing drug treatments with placebo and no-treatment conditions, which used objective sleep parameters or subjective sleep quality evaluations. Eight studies (152 participants) were included in the meta-analysis and involved trials using acetazolamide, temazepam, zolpidem, zaleplon, and theophylline. Generally, the nonbenzodiazepines were reported to be superior and safe in improving sleep quality. Participants who were administered zaleplon or zolpidem reported a significant improvement in subjective sleep quality. As measured by polysomnography, both zaleplon and zolpidem improved the total sleep time, sleep efficiency index, and stage 4 sleep duration, whereas they decreased the wake-after-sleep onset without impairing ventilation. In contrast, temazepam was not superior to placebo in terms of quicker onset of sleep and better sleep quality. On the other hand, acetazolamide and theophylline both reduced the sleep efficiency index. The present results favored zaleplon and zolpidem in improving both the objective and subjective quality of sleep without impairing ventilation. (c) 2018 Elsevier B.V. All rights reserved.