Objective: The interaction of 15 variables representing physical characteristics, previous altitude exposure, and ascent data was analyzed to determine their contribution to acute mountain sickness (AMS). Methods: Questionnaires were obtained from 359volunteers upon reaching the summit of Mt Whitney (4419m). Heart rate and arterial oxygen saturation were measured with a pulse oximeter, and AMS was identified by Lake Louise Self-Assessment scoring. Multiple logistic regression analysis was used to identify significant protective and risk factors for AMS. Results: Thirty-three percent of the sample met the criteria for AMS. The odds of experiencing AMS were greater for those who reported a previous altitude illness (adjusted odds ratio [OR] = 2.00, P<.01) or who were taking analgesics during the ascent (adjusted OR = 2.09, P<.01). Odds for AMS decreased with increasing age (adjusted OR = 0.82, P<.0001), a greater number of climbs above 3000m in the past month (adjusted OR = 0.92, P<.05), and use of acetazolamide during the ascent (adjusted OR = 0.33, P<.05). Conclusions: The significant determinants of AMS on the summit of Mt Whitney were age, a history of altitude illness, number of climbs above 3000m in the past month, and use of acetazolamide and analgesics during ascent.