Short exposures to severe or moderate hypoxia can have detrimental effects on postural stability. We hypothesized that continuous 24-h exposure to simulated 4300-m altitude (446 mmHg) would adversely affect postural stability and that this change in postural stability would be related to the severity of acute mountain sickness (AMS). On two different studies with similar experimental designs, postural instability was measured after approximately 3 and approximately 24 h of exposure using a computer-controlled unstable platform system in a total of 19 volunteers on three consecutive, 30-sec tests: eyes open (EO), eyes closed (EC), and a dynamic test involving tracking a circular moving object. Compared to baseline sea-level results, increases in postural instability were obtained with the EO test after 2 to 3 h (30%, p = 0.002) and 23 to 24 h (21%, p = 0.036) of altitude exposure. Similar increases were obtained on the EC test: 2 to 3 h (25%, p < 0.001) and 23 to 24 h (31%, p < 0.001). Although absolute instability values were higher on the EC test, the ratio EC/EO and the relative temporal changes with altitude exposure were similar. There were no significant altitude-stability effects on the target-tracking task. Sixty-three percent of the subjects (12 of 19) exhibited significant AMS (> 0.7 ESQ-C score) at some point during the 24-h exposure. No statistically significant correlations were obtained between the ESQ-C and any of the postural instability tests. These results indicate that postural stability is adversely affected during a 24-h exposure to 4300 m; however, there does not appear to be a correlation with the incidence or severity of AMS.