Psoriasis is a chronic condition with serious quality-of-life ramifications. Dermatologists seek alternative treatments of patients with plaque psoriasis that provide both efficacy and safety while minimizing exposure to high-potency steroids that can have adverse effects following long-term use. We report an open-label, multicenter study designed to evaluate a morning/evening (AM/PM) treatment regimen involving clobetasol propionate spray 0.05% and calcitriol ointment 3 μg/g for moderate plaque psoriasis. Participants applied clobetasol propionate spray 0.05% in the morning and calcitriol ointment 3 μg/g in the evening for up to 4 weeks. Participants were evaluated at baseline, week 2, and week 4. The results of this study indicate that a 4-week regimen of clobetasol propionate spray 0.05% treatment in the morning and calcitriol ointment 3 μg/g in the evening is efficacious and without unexpected safety issues for the management of moderate plaque psoriasis.