This study determined the effectiveness of 6 days (d) of staging at 2200 m on physiologic adjustments and acute mountain sickness (AMS) during rapid, high-risk ascent to 4300 m. Eleven sea-level (SL) resident men (means +/- SD; 21 +/- 3 yr; 78 +/- 13 kg) completed resting measures of end-tidal CO(2) (Petco(2)), arterial oxygen saturation (Sao(2)), heart rate (HR), and mean arterial pressure (MAP) at SL and within 1 h of exposure to 4300 m in a hypobaric chamber prior to 6 d of staging at 2200 m (preSTG) and on the summit of Pikes Peak following 6 d of staging at 2200 m (postSTG). Immediately following resting ventilation measures, all performed submaximal exercise ( approximately 55% of altitude-specific maximal oxygen uptake) for approximately 2 h on a bicycle ergometer to induce higher levels of AMS. AMS-C, calculated from the Environmental Symptoms Questionnaire, was measured following 4 h and 8 h of exposure at preSTG and postSTG, and the mean was calculated. Resting Petco(2) (mmHg) was unchanged from SL (39.8 +/- 2.6) to preSTG (39.3 +/- 3.0), but decreased (p < 0.05) from preSTG to postSTG (32.8 +/- 2.6). Resting Sao(2) (%) decreased (p < 0.05) from SL (97 +/- 2) to preSTG (80 +/- 4) and increased (p < 0.05) from preSTG to postSTG (83 +/- 3). Resting HR (bpm) and MAP (mmHg) did not change in any of the test conditions. The incidence and severity of AMS-C decreased (p < 0.05) from preSTG (91 +/- 30%; 1.05 +/- 0.56) to postSTG (45 +/- 53%; 0.59 +/- 0.43), respectively. These results suggest that modest physiologic adjustments induced by staging for 6 d at 2200 m reduced the incidence and severity of AMS during rapid, high-risk ascent to 4300 m.