A PaO2/FiO2 ratio (PFR) above 300 is a primary donor criterion for lung transplantation. Absence of cough and respiratory drive in the brain-dead (BD) donor results in basilar atelectasis, contributing to V/Q mismatching and hypoxemia. We hypothesized that ventilating BD donors in the prone position would result in better V/Q matching, increased PFR, and more lungs transplanted. All BD donors at our OPO are treated with a lung-protective ventilation strategy, recruitment maneuvers and repeated fiberoptic bronchoscopy (FOB). Since June 2018, a prone ventilation protocol was instituted for donors meeting the eligibility criteria: 12-70 years old, basilar atelectasis on X-ray or CT, and a PFR <300 after the first FOB. Eligible donors were placed in the prone position for at least 12 hours with all routine treatments continued. PFR was measured at four, eight, and twelve hours, as well as prior to procurement, and change calculated from baseline (∆PO2). The control group consisted of 81 hypoxemic donors treated with routine care in the supine position in the two years prior. In 14 months, 27 donors met eligibility criteria and were enrolled. Median baseline PFR was 222 mm Hg (IQR 181-270) compared to 187 (116-250) in controls (p=0.06). PFR increased more after four hours of prone ventilation (102 vs. 54 mm Hg, p=0.01), to 348 mm Hg (269-409) versus 264 (156-339) with supine ventilation. At 12-hours, there was a trend for PFR to remain higher: 351 (260-434) vs. 280 (157-358, p=0.13). Final PFR was 385 mm Hg (328-424) vs. 289 mm Hg (219-440, p=0.09) although ∆PO2 was comparable. However, more lungs were transplanted in the prone group (14 of 27 donors, 52%) compared to 23% in the control group, an effect persisting after adjusting for baseline PFR (OR 3.0, 95% CI: 1.2-7.8, p=0.02). Prone ventilation acutely improved oxygenation in hypoxemic BD organ donors with basilar atelectasis relative to those managed in the supine position and resulted in more lungs transplanted.