Abstract Disclosure: J.M. Brown: Consulting Fee; Self; Bayer, Inc. B. Bacare: None. Y.M. Niebuhr: None. L.C. Tsai: None. E.E. Abel: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; Corcept Therapeutics, HRA Pharmaceuticals, Mineralys. Context: Primary aldosteronism (PA) is a prevalent but grossly underrecognized contributor to the global burden of hypertension, excess cardiovascular and renal disease, and death. Though Endocrine Society guidelines recommend high risk populations who should be screened for PA, fewer than 2% of these at-risk patients are ever tested. Given the poor rates of routine screening within guideline-eligible populations, we designed and implemented a direct-to-patient virtual-based PA screening intervention. Methods: Participants with one or more guideline indications for PA screening were recruited using social media, online recruitment platforms, and online patient portals to participate in a video visit to review medical history and to arrange a local reference lab draw for plasma renin activity (PRA), aldosterone (via LC-MS/MS), and a basic metabolic panel, without adjustment of medications. Screening results were categorized as “Likely Confirmed PA”, “Possible PA”, or “Unlikely PA” based on established diagnostic frameworks. Test results, their interpretations, and possible next clinical steps (i.e., further testing, referral, empiric treatment) were communicated directly to patients and their primary care providers, with annual reminders and follow-up. Results: To date, 3220 participants from 12 states in the eastern USA had been contacted, with 2504 eligible. At the time of submission, 212 participants had completed laboratory assessment, with the remainder pending. 79 (37.3%) participants had resistant hypertension, 95 (44.8%) had hypertension with hypokalemia, 75 (35.4%) had hypertension with sleep apnea, 11 (5.2%) had hypertension with adrenal mass, and 90 (42.5%) had hypertension with a family history of early hypertension and/or stroke. Indicated PA screening had not previously been performed despite access to specialist care: 55% had an endocrinologist, cardiologist, and/or nephrologist. 27.4% of the participants had screening results consistent with either “likely confirmed PA” (7.1%) or “possible PA” (20.3%). Of those with both resistant hypertension and hypokalemia, 35.0% met criteria for “likely confirmed” or “possible” PA. A “likely confirmed” diagnosis of PA was associated with a median aldosterone-to-renin ratio of 33 ng/dL per ng/mL/h [IQR: 24, 76] and prevalent cardiometabolic comorbidities (33.3% had diabetes, 20.0% coronary artery disease, 13.3% heart failure). Conclusions: This ongoing, prospective, virtual-based, direct-to-patient PA screening program identified confirmed or possible PA in up to 27.4% of guideline-eligible participants. By reaching patients directly, rather than relying on routine clinical screening that is known to be dramatically underutilized, this study highlights the unrecognized prevalence of PA and demonstrates a novel approach to identifying this common, morbid, and treatable condition across the USA. Presentation: Friday, June 16, 2023