Background: Acne is a multifactorial disease in which androgens appear to play an important role. A low-dose oral contraceptive containing 20 μg of ethinyl estradiol and 100 μg of levonorgestrel (EE/LNG) has been shown to improve biochemical markers of androgenicity. Lowering bioavailable androgens may improve acne. Objective: The aim of this study was to evaluate the efficacy and safety of a low-dose oral contraceptive containing 20 μg of EE and 100 μg of LNG for the treatment of moderate acne. Methods: In a randomized, double-blind, placebo-controlled clinical trial, healthy female subjects (n = 371; ≥14 years old) with regular menstrual cycles and moderate facial acne were randomly assigned to receive EE/LNG or placebo for 6 cycles of 28 days. Acne lesion counts and clinician global assessment were performed at the end of each cycle. Patient self-assessments were collected and biochemical markers of androgenicity were also measured. Results: At the end of the study, the number of inflammatory and total lesions was significantly lower with EE/LNG compared with placebo (P < .05). Patients in the EE/LNG group also had significantly better scores for clinician global and patient self-assessments than those in the placebo group (P < .05). Biochemical markers of androgenicity improved during EE/LNG treatment compared with placebo and baseline values. Conclusion: A low-dose oral contraceptive containing EE/LNG is effective and safe for the treatment of moderate acne.