We evaluated in this study the efficacy and safety of an alternate regimen using clobetasol propionate 0.05% shampoo (CP shampoo) for long-term control of scalp psoriasis. Patients with moderate scalp psoriasis (Global Severity Score [GSS] of 3 on a 0-5 scale) first received CP shampoo once daily for 4 weeks. Patients with a GSS <or= 2 were then randomized into the maintenance phase, receiving CP shampoo or vehicle twice weekly. When relapse (GSS > 2) occurred, patients received the 4-week daily CP shampoo treatment. Patients who had a GSS <or= 2 afterwards reinitiated the twice-weekly maintenance according to the original randomization scheme. Among the 168 patients enrolled, 141 (83.9%) had a GSS <or= 2 after the initial phase. The median time to first relapse was 141 days with CP shampoo, almost 4 months later than with vehicle (30.5 days;p < 0.0001). After 6 months, the percentage of patients who had no relapse was significantly higher with CP shampoo (40.3%) than with vehicle (11.6%;p < 0.001). CP shampoo was also safe during the 7-month study period, without leading to more cases of skin atrophy, telangiectasia, hypothalamic-pituitary-adrenal (HPA) axis suppression or adverse events compared to vehicle. The alternate treatment regimen with CP shampoo is efficacious and safe for long-term management of moderate scalp psoriasis.