Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness (AMS) during gradual ascent. This trial was designed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent. In this double-blind, randomized, placebo-controlled trial, 26 participants residing at sea level received ginkgo (60 mg TID) or placebo starting 24 h before ascending Mauna Kea, Hawaii. Subjects were transported from sea level to the summit (4205 m) over 3 hours, including 1 hour at 2835 m. The Lake Louise Self-report Questionnaire constituted the primary outcome measure at baseline, 2835 m, and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score (LLSR) >/= 3 with headache. Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study. The ginkgo (n = 12) and placebo (n = 14) groups were well matched (58% vs. 50% female; median age 28 yr, range 22-53 vs. 33 yr, range 21-53; 58% vs. 57% Caucasian). Two (17%) subjects on ginkgo and nine (64%) on placebo developed severe AMS and required descent for their safety (p = 0.021); all recovered without sequelae. Median LLSR at 4205 m was significantly lower for ginkgo versus placebo (4, range 1-8 vs. 5, range 2-9, p = 0.03). Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo (ginkgo 7/12, 58.3% vs. placebo 13/14, 92.9%, p = 0.07). Twenty-one of 26 (81%) subjects developed AMS overall. This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 m.