Background: Both calcipotriene and tazarotene have been shown to be effective in the treatment of psoriasis. No study has evaluated the effect of using both agents simultaneously. Objective: Our purpose was to evaluate the effectiveness of combination treatment of psoriasis with calcipotriene ointment and tazarotene gel by comparing them with clobetasol ointment, a class I topical corticosteroid. A secondary objective was to evaluate the clinical compatibility of applying both agents at the same time. Methods: This pilot study was a prospective, single-center, open-label, right/left comparison of 28 lesion pairs in 15 patients. It consisted of a 2-week treatment phase, followed by a 4-week post-treatment observation phase. Results: All 15 patients completed the treatment phase of the study. At the end of the active treatment phase (end of week 2), calcipotriene- and tazarotene-treated lesions showed nearly identical reductions in scaling (P = .93), plaque elevation (P = .76), and overall lesional severity scores (P = .29) compared with their matched clobetasol-treated counterparts. Erythema improved significantly more in clobetasol-treated lesions (P < .05) during the treatment period, but differences became statistically insignificant during the post-treatment period (;P = .20). No patients had significant irritation from the treatments. During the post-treatment phase (weeks 3-6), all lesions worsened; plaque elevation returned somewhat more rapidly in calcipotriene- and tazarotene-treated lesions (P < .01), whereas changes in scaling, erythema, and overall lesional severity were not significantly different between the two treatment groups (P > .05). Conclusion: The nonsteroid combination of twice-daily calcipotriene ointment and once-daily tazarotene gel was not statistically different from twice-daily application of the class I corticosteroid clobetasol ointment in reducing psoriatic scaling, plaque elevation, and overall lesional severity over a 2-week period. There does not seem to be any chemical incompatibility between calcipotriene ointment and tazarotene gel that is clinically significant. (J Am Acad Dermatol 2002;46:907-13.)