This study compared the efficacy of a low-dose combined oral contraceptive (COC) containing 3-mg drospirenone and 20-microg ethinyl estradiol (3-mg DRSP/20-microg EE) administered in a 24-day active pill/4-day inert pill (24/4) regimen and placebo in women with moderate acne vulgaris during 6 treatment cycles. A total of 534 participants were randomized and dispensed study medication (n = 266 [3-mg DRSP/20-microg EE 24/4 regimen COC group]; n = 268 [placebo group]). Women of reproductive age were eligible for inclusion in the study. Treatment with the 3-mg DRSP/20-microg EE 24/4 regimen COC was associated with a greater reduction from baseline to end point in individual lesion counts (papules, pustules, open and closed comedones) compared with placebo. The mean nodule count remained essentially constant throughout the study and was low in both treatment groups. There was a significantly higher probability that a participant had an improved assessment on the investigator's overall improvement rating scale (odds ratio [OR], 4.02; 95% CI [confidence interval], 2.29-7.31; P < .0001) and participant's overall self-assessment rating scale (OR, 2.82; 95% CI, 1.60-5.13; P = .0005) in the 3-mg DRSP/20-microg EE 24/4 regimen COC group than in the placebo group. The COC 3-mg DRSP/20-microg EE 24/4 regimen is a suitable option for women with moderate acne vulgaris who require contraception.