Background: The use of Cardiopulmonary Bypass (CPB) in lung transplantation remains controversial. The goal of this study was to determine whether lung transplant with CPB affects lung function or development of bronchiolitis obliterans compared to off pump patients. Methods: After IRB approval, a review of 151 patients who underwent orthotopic lung transplant with either CPB or off pump sequential placement was compared. Demographic data, bypass times, total surgery, intubation times and ICU stay were recorded. Biopsy determined rejection was compared, along with FEV1 changes from immediate post-transplant values. Significant differences between groups were determined at p < 0.05. Results: Demographic variables were similar. CPB was associated with longer postoperative ventilation (4.8 vs 2.3 days) p=.07. 56% of bypass patients, vs 39% of non-bypass, showed no evidence of rejection. CPB patients also had less single rejection episodes 20% vs 30%. FEV1 improved from baseline over the first year in both groups and improved over the next two years after transplant (12.4, 19.1, 19.4 vs, 7.3, 11.2, 10.6) CPB vs non-bypass respectively p = 0.034. Conclusion: Cardiopulmonary bypass appeared to have no deleterious effect on FEV1 or rejection. CPB may provide a protective mechanism with reduced rejection after lung transplantation