A multicenter, investigator-masked, randomized, parallel-group study was performed in 440 patients with mild-to-moderate facial acne vulgaris to compare the efficacy and tolerability of tazarotene monotherapy with 3 combination regimens--tazarotene plus benzoyl peroxide gel, tazarotene plus erythromycin/benzoyl peroxide gel, and tazarotene plus clindamycin phosphate lotion. An additional treatment group-monotherapy with clindamycin phosphate lotion-also was included as a reference arm. The only combination therapy to achieve a significantly greater global improvement than tazarotene monotherapy was tazarotene plus clindamycin. For reducing noninflammatory lesions specifically, none of the combination regimens offered significant benefit over tazarotene monotherapy (though tazarotene plus clindamycin and tazarotene plus erythromycin/benzoyl peroxide were significantly more efficacious than clindamycin monotherapy). For reducing inflammatory lesions, tazarotene plus erythromycin/benzoyl peroxide was significantly more efficacious than all the other regimens. Although tazarotene plus clindamycin and tazarotene plus benzoyl peroxide reduced the incidence of adverse effects compared with tazarotene monotherapy, the difference did not achieve statistical significance.