We conducted a randomized double-blind study of 32 subject with acute ankle sprains to compare treatment with hyperbaric oxygen at 2 atmospheres absolute pressure (N = 16) (treatment group) with treatment with air at 1.1 atmosphere absolute pressure (N = 16) (control group) in a hyperbaric chamber. Each group received three treatments at their respective pressures: one for 90 minutes and two for 60 minutes each. Mean age, severity grade, and time to treatment (treatment group, 34.3 +/- 6.3 hours; control group, 32.6 +/- 4.6 hours) were similar in both groups. Joint function measured by a functional index improved from 0.40 +/- 0.2 to 6.3 +/- 0.4 with hyperbaric oxygen and from 0.8 +/- 0.3 to 5.3 +/- 0.6 with air. The change from initial to final evaluation was significantly greater in the treatment group. Foot and ankle volume by water displacement decreased from 1451 +/- 57 ml to 1425 +/- 63 ml with hyperbaric oxygen and from 1403 +/- 50 ml of 1371 +/- 45 ml with air (no difference was noted between hyperbaric oxygen treatment and air treatment using a two-day analysis of variance). Subjective pain index fell from 3.3 +/- 0.5 to 0.8 +/- 0.3 with hyperbaric oxygen and from 2.6 +/- 0.3 to 0.3 +/- 0.2 with air. No differences were noted in passive or active range of motion when comparing hyperbaric oxygen treatment with air treatment. Time to recovery was the same in both groups (treatment, 16.0 +/- 6.3 days; control, 15.4 +/- 2.8 days). Regression analysis to determine the influence of time to treatment, initial severity of injury, hyperbaric oxygen, and age showed no effect of hyperbaric oxygen treatment on time to recovery.