SummaryBackgroundThe saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA) whilst adrenal vein sampling (AVS) is used to determine whether the aldosterone hypersecretion is unilateral or bilateral. An accurate prediction of bilateral PA based on SST results could reduce the need for AVS.AimWe sought to identify SST parameters that reliably predict bilateral PA.MethodsThe results from 121 patients undergoing SSTs at Monash Health from January 2010 to January 2018 including screening blood tests, imaging, AVS and histopathology results were evaluated. Patients were subtyped into unilateral or bilateral PA based on AVS and surgical outcomes.ResultsOf 113 patients with confirmed PA, 33 had unilateral disease whilst 42 had bilateral disease. In those with bilateral disease, plasma aldosterone concentration (PAC) was significantly lower post‐SST, together with a significant fall in the aldosterone‐renin ratio (ARR). The combination of PAC < 300 pmol/L and a reduction in ARR post‐SST provided 96.8% specificity in predicting bilateral disease. Eighteen of 39 patients (49%) with bilateral PA could have avoided AVS using these criteria.ConclusionA combination of PAC < 300 pmol/L and a lower ARR post‐SST could reliably predict bilateral PA. An independent cohort will be needed to validate these findings.