Introduction: Reports on intraocular pressure (IOP) changes at high altitudes have revealed inconsistent and even conflicting RESULTS: The aim of this study was to investigate the effect of very high altitude and different ascent profiles on IOP in relation to simultaneously occurring ophthalmic and systemic changes in a prospective study. Methods: Prospective study in 25 healthy mountaineers who were randomly assigned to two different ascent profiles during a medical research expedition to Mt Muztagh Ata (7546m/24751ft). Group 1 was allotted a shorter acclimatization time prior to ascent than Group 2. Besides IOP, oxygen saturation (SaO2), acute mountain sickness symptoms (AMS-c score) and optic disc appearance were also assessed. Examinations were performed at 490m/1607ft, 4497m/14750ft, 5533m/18148ft and 6265m/20549ft above sea level. Results: Intraocular pressure in both groups showed small but statistically significant changes: an increase during ascent from 490m/1607ft to 5533m/18148ft and then a continuous decrease during further ascent to 6265m/20549ft and upon descent to 4497m/14750ft and to 490m. Differences between groups were not significant. Multiple regression analysis (IOP dependent variable) revealed significant partial correlation coefficient of Beta= -0.25 (p=0.01) for SaO2,and Beta = -0.23 (p=0.02) for acclimatization time. Discussion: Hypobaric hypoxia at very high altitude leads to small but statistically significant changes in IOP that are modulated by systemic oxygen saturation and correlate with optic disc swelling. Climbs to very high altitudes seem to be safe with regard to intraocular pressure changes.