Abstract Context The Endocrine Society Guidelines for the diagnosis of primary aldosteronism (PA) suggest that confirmatory tests (CFT) are not required when the following criteria are met: plasma aldosterone concentration (PAC) is >20 ng/dL, plasma renin is below detection levels, and hypokalemia is present. The evidence for the applicability of the guideline criteria is limited. Objective To develop and validate optimized criteria for sparing CFT in the diagnosis of PA. Design and Setting The optimized criteria were developed in a Chinese cohort using the captopril challenge test, verified by saline infusion test (SIT) and fludrocortisone suppression test (FST), and validated in an Australian cohort. Participants Hypertensive patients who completed PA screening and CFT. Main Outcome Measure Diagnostic value of the optimized criteria. Results In the development cohort (518 PA and 266 non-PA), hypokalemia, PAC, and plasma renin concentration (PRC) were selected as diagnostic indicators by multivariate logistic analyses. The combination of PAC >20 ng/dL plus PRC <2.5 μIU/mL plus hypokalemia had much higher sensitivity than the guideline criteria (0.36 vs 0.11). The optimized criteria remained superior when the SIT or FST were used as CFT. Non-PA patients were not misdiagnosed by either criteria, but the percentage of patients in whom CFT could be spared was higher with the optimized criteria. In the validation cohort (125 PA and 81 non-PA), the sensitivity of the optimized criteria was also significantly higher (0.12 vs 0.02). Conclusions Hypertensive patients with PAC >20 ng/dL, PRC <2.5 μIU/mL, plus hypokalemia can be confidently diagnosed with PA without confirmatory tests.