Occlusive therapy with or without topical agents is effective in the treatment of psoriasis. This study assessed the efficacy and safety of an occlusive hydrogel dressing. Participants were treated with calcipotriene 0.005%–betamethasone dipropionate 0.064% ointment with and without a hydrogel patch. Thirty participants completed the 6-week, bilaterally controlled, investigator-blinded, single-center study. Substantial reductions in total modified psoriasis area and severity index (PASI) scores of occluded lesions versus nonoccluded lesions were seen as early as the first week of treatment and sustained through 4 weeks of the study. No adverse effects related to the study, including skin irritation, were observed or reported. Hydrogel dressings provide an effective and safe occlusive option to enhance topical therapy for psoriasis.