BACKGROUND: A novel topical foam formulation of ketoconazole has been developed for use on the scalp, body, and face. OBJECTIVE: To evaluate the efficacy and safety of twice-daily treatment with ketoconazole 2% foam for seborrheic dermatitis on the scalp, body, and face. METHODS: One thousand one hundred sixty-two subjects, aged 12 years or older, with mild to severe seborrheic dermatitis were randomized to receive ketoconazole foam (n=427), vehicle foam (n=420), ketoconazole cream (n=210), or vehicle cream (n=105) twice daily for 4 weeks. The primary endpoint was the proportion of subjects achieving an Investigator's Static Global Assessment score of 0 or 1 at week 4 (treatment success). RESULTS: A significantly greater percentage of subjects achieved treatment success using ketoconazole foam than vehicle foam (56% and 42%, respectively; P<.0001); ketoconazole foam was shown to be equivalent to ketoconazole cream. Ketoconazole foam was well-tolerated with a low incidence of treatment-related adverse events (14%; 59/427). CONCLUSION: Ketoconazole foam 2% is a safe, effective, and versatile formulation for use on the scalp, body, and face for the treatment of seborrheic dermatitis in patients aged 12 years or older.