Study Objectives: Sleep is altered at high altitude leading many mountaineers to use hypnotics in order to improve sleep efficiency. While after a full night at altitude the short-acting hypnotic zolpidem does not appear to alter cognitive function, residual adverse effects should be considered following early waking-up as performed by mountaineers. We hypothesized that zolpidem intake at high altitude would alter cognitive function 4 hours after drug intake. Methods: In a randomized double-blind controlled cross-over study, 22 participants were evaluated during two nights at sea level and two nights at 3800 m, 4 hours after zolpidem (10 mg) or placebo intake at 10:00 pm. Polygraphic recording was performed until waking-up at 01:30 am. Sleep quality, sleepiness and symptoms of acute mountain sickness were assessed by questionnaires. Two cognitive tasks (Simon task and durationproduction task) were performed at rest and during exercise and postural control was evaluated. Results: Zolpidem increased reaction time in all conditions (zolpidem 407 +/- 9 ms vs. placebo 380 +/- 11 ms; p < 0.001) and error rate in incongruent trials only (10.2 +/- 1.1% vs. 7.8 +/- 0.8%; p < 0.01) in the Simon task and increased time perception variability (p < 0.001). Zolpidem also altered postural parameters (e. g. center of pressure area, zolpidem 236 +/- 171.5 mm(2) vs. placebo 119.6 +/- 59 mm(2); p < 0.001). Zolpidem did not affect apnea-hypopnea index and mean arterial oxygen saturation (p > 0.05) but increased sleep quality (p < 0.001). Zolpidem increased symptoms of acute mountain sickness and sleepiness (p < 0.05). Conclusions: Acute zolpidem intake at high altitude alters cognitive functions and postural control during early wakening which may be deleterious for safety and performances of climbers.