This study was designed to evaluate the safety and efficacy of concomitant therapy with the corticosteroid clocortolone pivalate cream 0.1% (Cloderm® Cream 0.1%) and the topical immunosuppressive agent tacrolimus ointment 0.1% (Protopic® Ointment 0.1%) and to compare each drug alone for the treatment of atopic dermatitis in adolescents and adults. Concomitant therapy may minimize the potential adverse effects of both treatments taken alone and may potentially improve overall response. In this 21-day study with 57 patients with atopic dermatitis, groups of 19 patients were randomized to 1 of 3 treatments: concomitant treatment with clocortolone pivalate cream 0.1% and tacrolimus ointment 0.1% (CPC+TO), monotherapy with clocortolone pivalate cream 0.1% (CPC), or monotherapy with tacrolimus ointment 0.1% (TO). CPC+TO was statistically superior to TO alone in the percentage change for dermatologic sum score at days 14 (P=.024) and 21 (P=.033), excoriation at day 21 (P=.028), induration at day 21 (P=.033), and erythema at day 14 (P=.048). The dual therapy was also superior to CPC alone in excoriation at days 7 (P=.045) and 14 (P=.037), oozing or crusting at days 3 (P=.034) and 7 (P=.012), and lichenification at day 3 (P=.031). In addition, unlike the 2 single-therapy treatment groups, percentage reductions from baseline in scores for the sensation of transient pruritus and burning or stinging were statistically significant for the concomitant treatment at days 14 (P=.016) and 21 (P=.016).