Acute mountain sickness (AMS) is the most common form of altitude illness affecting athletes and adventurists who work or play at elevations greater than 10,000 ft above mean sea level. Considerable research has been conducted to mitigate risk for those who work or play in environmental extremes. This article describes the experiences of a group of U.S. Army Special Operations soldiers who tested recommended doses of acetazolamide prophylaxis for AMS during six expeditions to elevations between 19,000 and 23,000 ft. In addition, we briefly review the literature as it pertains to prophylaxis of AMS. In our experience, prophylaxis with the recommended doses of acetazolamide resulted in fewer AMS symptoms and seemed to confer a higher likelihood of successfully summiting each peak. We conclude that acetazolamide is an acceptable choice for AMS prevention along with a slow, controlled ascent and proper fitness, nutrition, clothing, and gear.