Purpose Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies of PGD risk factors have produced conflicting results due to small sample sizes, inconsistencies in PGD phenotype, inability to control for multiple confounders, and use of retrospective, single center, or administrative data. We sought to identify donor, recipient, and peri-operative risk factors for PGD. Methods and Materials We performed a 10 center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was grade 3 PGD at 48 or 72 hrs post transplant. The association of risk factors with PGD was analyzed using multivariable conditional logistic regression. Results 1255 patients were enrolled; 211 subjects (16.8%) developed PGD. In multivariable models, risk factors for PGD were any history of donor smoking (OR=1.8, 95%CI 1.2, 2.6, p=0.002), FiO2 at allograft reperfusion (OR=1.1 per 10% increase in FiO2, 95%CI 1.0, 1.2; p=0.01), single lung transplant (OR=2.0, 95%CI 1.2, 3.3; p=0.008), cardiopulmonary bypass (OR=3.4, 95%CI 2.2, 5.3; p Conclusions We identified important PGD risk factors, including donor smoking, recipient factors of pre-transplant diagnosis and BMI, and perioperative treatment variables, including use of cardiopulmonary bypass, blood transfusion volume, and FiO2 at reperfusion. Several of these risk factors are potentially modifiable, and thus may suggest preventative strategies, while other risk factors should be prioritized for future mechanistic research efforts.