Acute mountain sickness (AMS) in high altitude trekkers is common, often trek-limiting, and occasionally fatal. The incidence of AMS can be modified by prudent ascent profile and route selection. It is not known whether the 6-day Machame route may enhance acclimatization on Kilimanjaro (5895 m) by 'sleeping low' on the third day. This report presents real time twice-daily AMS data from 28 healthy adult trekkers on the Machame route. The incidences of AMS and severe AMS were: 0% and 0% (day 1); 11% and 4% (day 2); 25% and 4% (day 3); 25% and 0% (day 4); 86% and 61% (summit day 5); and 7% and 0% (day 6), respectively. High altitude cerebral edema occurred in 4 of 28 trekkers (14%). On summit day, the median Lake Louise Symptom Score (LLSS) was 8 (range 2 to 15). Twice-daily measurements of AMS symptoms provide detailed insight into the time-course and evolution of AMS during ascent on Kilimanjaro. The 6-day Machame route may delay the onset but does not ultimately protect against AMS. The extremely high incidence and severity of AMS on summit day is of major concern to trekkers, portering staff, expedition medical staff, and leaders.