Ex vivo lung perfusion (EVLP) allows for the evaluation and treatment of donor lungs before transplant. Different EVLP strategies have been described using either an open left atrium (LA) (pressure of 0 mm Hg) or closed LA (pressure of 5 mm Hg). We hypothesized that maintaining a physiologic positive LA pressure during EVLP is protective to the lung. Pig lungs were flushed with Perfadex, retrieved and stored at 4°C for 4 hours [short cold ischemic time (CIT), n = 10] or 18 hours (prolonged CIT, n = 8). Subsequently, lungs underwent normothermic EVLP for 12 hours using either an open or closed LA technique. A linear mixed effect model was used to compare functional parameters between the 2 groups. After short CIT, 12-hour EVLP could not be completed in 4 of 5 open atrium cases due to significant pulmonary edema. Lung injury was evident in this group after 7 hours of EVLP, demonstrating an increase in pulmonary vascular resistance (p < 0.001) and peak inspiratory pressure (p = 0.001), and a decrease in lung compliance (p < 0.001) and perfusate oxygenation (p = 0.04). In contrast, in the closed atrium group, all lungs completed 12 hours of EVLP with stable functional parameters. At the end of the experiment, the wet/dry ratio (p = 0.015) and lung edema score (p = 0.02) were significantly worse in the open LA group compared with the closed LA EVLP group. Similar findings were observed in the prolonged CIT group. The use of a closed atrial technique to create a controlled positive LA during EVLP leads to significantly less edema and superior lung physiology.