Background: The merit of topical sequential therapy involving clobetasol foam and calcipotriene ointment has not been experimentally demonstrated. Objective: We sought to assess the short-term efficacy of twice-daily clobetasol foam plus calcipotriene ointment compared with either agent alone as monotherapy and to compare long-term use of weekday calcipotriene ointment with or without clobetasol foam weekend pulse therapy. Methods: Eighty-six subjects with plaque-type psoriasis received twice-daily treatment with clobetasol foam plus calcipotriene ointment or either agent as monotherapy for 2 weeks. Subjects in the combination group who achieved remission received weekday calcipotriene plus weekend pulse therapy with either clobetasol foam or vehicle for 6 months. Results: After 2 weeks, psoriasis scores were significantly lower (P < .001) in the combination therapy group (adjusted trunk lesion score = 0.67) compared with monotherapy with either agent (lesion scores = 1.40 calcipotriene, 1.13 clobetasol foam). During the follow-up "weekday-weekend" phase, after 6 months, weekend pulse clobetasol foam was associated with a trend toward greater maintenance of remission compared with vehicle (92% improvement of trunk lesion vs 62%). Limitations: Small sample size may have hampered the detection of statistical significance during long-term therapy. Conclusion: The combination of clobetasol foam and calcipotriene ointment is significantly more effective than monotherapy for short-term treatment. Weekday calcipotriene plus weekend pulse clobetasol foam shows a consistent trend toward greater maintenance of remission.