Introduction: Drospirenone (DRSP) is a novel progestin with antimineralocorticoid and antiandrogenic activities.Methods: In this open-label, multicenter study, 322 healthy women aged 18 to 35 years used a monophasic oral contraceptive consisting of 30 μg ethinyl estradiol (EE) and 3 mg DRSP for six cycles. Subjects completed a 23-item Women's Health Assessment Questionnaire (WHAQ) at baseline and at the end of the sixth cycle. The WHAQ scored symptoms on a five-point scale during the premenstrual and menstrual phases and during the rest of the cycle (postmenstrual phase).Results: At baseline, mean scores for negative affect, water retention, and impaired concentration were higher during the premenstrual and menstrual phases than during the postmenstrual phase. At the end of cycle 6, premenstrual and menstrual symptom scores of negative affect and water retention were reduced significantly relative to baseline (P <0.001), with similar improvements seen among women who were new users of hormonal contraceptives (P <0.01) and those who switched from their previous contraceptives (P <0.001). Impaired concentration scores were not significantly reduced from baseline.Conclusions: These results suggest that an oral contraceptive containing DRSP/EE may reduce perimenstrual symptoms, notably those related to negative affect and water retention. A controlled, prospective trial in women with more severe perimenstrual symptoms is needed to confirm these findings.