PURPOSE: It is unclear whether mechanical ventilator settings impact the risk of primary graft dysfunction (PGD) after lung transplantation. Importantly, ventilator settings are typically based on recipient rather than donor weight and height. In this study, we examined the relationship between lung protective ventilation based on donor size and PGD. METHODS: We analyzed 373 adult bilateral lung transplant recipients at our center between 1/2010 and 1/2017. We collected recipient, donor, and ventilator data after transplantation. We defined PGD as PGD 3 between 24 and 72 hours after transplantation and lung protective ventilation as a maximum tidal volume <8ml/kg of donor ideal body weight and a maximum plateau pressure <30cmH2O. We used logistic regression to examine the relationship between maximum tidal volume and PGD 3 and lack of lung protective ventilation and PGD 3 separately. We examined the associations between known PGD risk factors including recipient and donor risk factors and ischemic time and PGD 3 using univariate analyses and included those that were significant in the multivariate analysis. RESULTS: In univariate analysis, maximum tidal volume expressed as ml/kg of donor ideal body weight was associated with a significantly increased risk of PGD 3, (OR=1.42; 95%CI = 1.12-1.72, p>0.001). Similarly, lack of lung protective ventilation was associated with a significantly increased risk of PGD 3 (OR=5.56; 95%CI = 1.89-16.34, p=0.002). PGD risk factors that were significant in the univariate analysis were included in the multivariate analysis. In multivariate analysis, maximum tidal volume remained an independent predictor of PGD 3. Similarly, lack of lung protective ventilation remained an independent predictor of PGD 3. CONCLUSION: Higher tidal volumes and not receiving lung protective ventilation were associated with an increased risk of PGD 3 between 24 and 72 hours. This suggests that adjusting ventilator settings based on donor size and lung protective ventilation after transplantation may mitigate the risk of PGD.