To investigate the invitro effect of drospirenone on human eutopic endometrial (EuSC) and ectopic endometriotic stromal cells (EcSC). Comparative and laboratory study. The experimental procedures were approved by the Institutional Review Board of the University of Tokyo (registration no. 0324-4). University research laboratory. Eight patients undergoing hysterectomy for benign gynecologic disease and 19 patients undergoing cystectomy or adnectomy for endometriosis. EuSC and EcSC were treated with drospirenone. For the analysis of decidualization of EuSC, cells were observed using microscopy, and the production of PRL was measured using enzyme immunoassay. For the analysis of DNA synthesis of EcSC, 5-bromo-2'-deoxyuridine incorporation was measured by ELISA. Cells in apoptosis were detected and measured by flow cytometry. Drospirenone induced decidualization in EuSC, and the induction was negated by RU486. Drospirenone reduced DNA synthesis on EcSC, and this reduction was negated by RU486 or P receptor silencing, but not by aldosterone or mineralocorticoid receptor silencing. Drospirenone did not cause EcSC to undergo apoptosis. Our study demonstrates the direct effects of drospirenone: decidualization of EuSC and reduced DNA synthesis of EcSC, but it does not cause EsSC apoptosis.