BACKGROUND: Pityriasis (tinea) versicolor has a high tendency to recur after being treated successfully. Prophylactic treatment to reduce recurrence is needed. OBJECTIVE: To determine whether recurrence of pityriasis versicolor could be prevented by prophylactic itraconazole treatment. DESIGN: Open treatment followed by a randomized, double-blind, placebo-controlled phase. SETTING: Multinational outpatient centers. PATIENTS: A total of 239 consecutive patients were included; 238 started open treatment. A total of 209 patients started prophylactic treatment: 106 in the itraconazole group and 103 in the placebo group. INTERVENTIONS: Open treatment: itraconazole, 200 mg once daily for 7 days. Prophylactic treatment: itraconazole, 200 mg, or placebo twice daily 1 day per month for 6 consecutive months. MAIN OUTCOME MEASURES: Mycological cure rates at the end of open treatment and at the end of prophylactic treatment. RESULTS: Mycological cure at the end of open treatment was 92% (205/223). At the prophylactic treatment end point (6 months), mycological cure was 88% (90/102) in the itraconazole group and 57% (56/99) in the placebo group (P<.001). In open treatment, 11 patients were not able to be evaluated for efficacy. In prophylactic treatment, 4 patients in the itraconazole group and 4 in the placebo group were not able to be evaluated. Adverse events were reported during open treatment by 26 patients (11%) and during prophylactic treatment by 17 (16%) in the itraconazole group and 14 (14%) in the placebo group. No patients experienced any serious adverse events. CONCLUSIONS: Prophylactic itraconazole treatment is efficacious for pityriasis versicolor after 6 months, as is itraconazole in the treatment of pityriasis versicolor.