BACKGROUND Primary aldosteronism is recognized as the most frequent cause of secondary hypertension. Screening for primary aldosteronism by determination of the aldosterone-to-renin ratio (ARR) is much more frequently performed in current practice. However, most antihypertensive medications interfere with ARR determination, and although verapamil and alpha-adrenergic blockers are considered sufficiently neutral, the specific drugs which should be discontinued before ARR screening are a matter of debate. Our objective was to evaluate the possible interference of a new progestin with antimineralocorticoid activity (drospirenone) on the determination of ARR and the diagnosis of primary aldosteronism. RESULTS We describe an instance of a false-positive laboratory diagnosis of primary aldosteronism (by both screening and confirmatory test) in a normotensive 34-year-old healthy woman taking Yasmin (drospirenone + ethinylestradiol) (Shering S.p.A., Milan, Italy). Subsequent ARR values during Yasmin therapy changed during the menstrual cycle (days 7, 14, 21, and 28 were tested), reaching values above the screening ARR threshold that led to a suspicion of primary aldosteronism just before menses. In contrast, during a drug-free menstrual cycle, the ARR remained constantly below the screening ARR threshold. CONCLUSIONS We report for the first time that drospirenone may interfere with laboratory screening and confirmatory testing for the diagnosis of primary aldosteronism. As a consequence, this drug should be withdrawn in hypertensive women investigated for secondary hypertension. Although drospirenone was demonstrated to possess antihypertensive properties when taken as postmenopausal hormonal replacement therapy, its use for contraceptive purposes needs to be more carefully investigated.