BACKGROUND Tinea versicolor is a common superficial fungal infection caused by a lipophilic yeast. This chronically recurring opportunistic infection is especially prevalent in tropical and semitropical regions. The topical short-term application of ketoconazole 2% shampoo may provide effective and safe therapy for tinea versicolor. OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of a single application (1 day) versus three daily applications (3 days) of ketoconazole 2% shampoo versus placebo shampoo in the treatment of mycologically confirmed tinea versicolor. METHODS Three hundred twelve patients were included in the primary analyses for this 31-day study. Global evaluation scores were measured on days 10 and 31 with a 5-point scale (1 = healed to 5 = worsening), and a cellophane tape test was done at baseline and days 3, 10, and 31. Efficacy was assessed by clinical response, defined as both a global evaluation score of 1 (healed) and a negative cellophane tape test on day 31. Signs and symptoms of tinea versicolor (scaling, itching, erythema, hypopigmentation, hyperpigmentation) also were evaluated at baseline, day 10, and day 31 with a 4-point scale (0 = absent to 3 = severe). RESULTS Both regimens of ketoconazole shampoo were significantly (P < .001) more effective than placebo for rate of clinical response, global evaluation scores, and mycologic outcomes (cellophane tape test). The clinical response rates at day 31 were 73%, 69%, and 5% for the 3-day ketoconazole, 1-day ketoconazole, and placebo groups, respectively. The difference in the efficacy of the two ketoconazole treatment regimens was not statistically significant. There were no significant differences between any of the treatment groups in the number of patients who experienced adverse events. No serious adverse events occurred and no patient withdrew from the trial prematurely because of an adverse event. CONCLUSIONS Ketoconazole 2% shampoo, used as a single application or daily for 3 days, is safe and highly effective in the treatment of tinea versicolor.