To investigate the determinants of acute mountain sickness (AMS) and of summiting in expedition-style mountaineering, 919 mountaineers (15.4% female) leaving Aconcagua Provincial Park at the end of an expedition to Mt. Aconcagua (6962 m) via the normal route were retrospectively evaluated by questionnaires. Symptoms of AMS were reported from the day when mountaineers felt worst. The prevalence of AMS, defined as a Lake Louise Score (self-assessment) > 4, was 39%. Low AMS scores were associated with faster ascent rates. The following parameters were independent predictors for AMS: no susceptibility for AMS (odds ratio, OR, 0.24; 95% confidence interval 0.17 to 0.35) more than 10 exposures per year above 3000 m (OR 0.60; 0.41 to 0.86), and previous exposures above 6000 m (OR, 0.48; 0.33 to 0.68). This last variable increased the OR for summiting 3.7-fold while female gender reduced this OR to 0.41 (0.25 to 0.67). Susceptibility and few exposures to high altitude are major predictors for AMS on Aconcagua, but AMS does not substantially reduce the chances for summiting. Those who are often in the mountains and who have already climbed to altitudes above 6000 m and are not susceptible for AMS have the best options for summiting Aconcagua.