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Primary aldosteronism is affecting about 10% of hypertensive patients. Primary aldosteronism should be diagnosed by screening tests based on plasma aldosterone concentration (PAC) and aldosterone-to-renin ratio (ARR), followed by confirmatory test. The cutoff values for PAC and ARR depend on PAC and plasma renin measurement methods. Liquid chromatography–tandem mass spectrometry (LC-MS/MS), the new gold standard method for aldosterone determination, is now widespread but shows lower values than immunoassays. New cutoff values have yet to be determined with LC-MS/MS PAC.In a retrospective cohort, we measured PAC by LC-MS/MS in 93 healthy volunteers, 77 patients with essential hypertension and 82 primary aldosteronism patients (42 lateralized, 24 bilateral, 16 primary aldosteronism without adrenal vein sampling) after 30 min in a seated position.PAC ranged from 42 to 309 pmol/l in healthy volunteers and from 63 to 362 pmol/l in essential hypertensive patients. A cutoff value of 360 pmol/l for basal PAC had a sensitivity of 90.5% and a specificity of 95.1% to differentiate lateralized primary aldosteronism from essential hypertensive patients. ARR ranged from 2.3 to 22.3 in healthy volunteers and from 3.2 to 55.6 pmol/mU in essential hypertensive patients. Using ROC curves, we selected an ARR of 46 pmol/mU, which provided a sensitivity of 100% and a specificity of 93.4% to distinguish between essential hypertensive and lateralized primary aldosteronism patients (sensitivity 94.4%, specificity 93.9% for the overall primary aldosteronism population).Criteria for primary aldosteronism screening need to be adapted, given the increasing use of LC-MS/MS to determine PAC. We suggest to use 360 pmol/l and 46 pmol/mU as cutoff values, respectively, for basal PAC and ARR after 30 min of seated rest.