OBJECTIVES: The role of intraoperative cardiopulmonary bypass (CPB) in lung transplant (LTx) surgery is controversial. CPB enables slow pulmonary reperfusion and initial ventilation with low oxygen concentrations, both theoretically protective of transplanted lungs. In this study, we explored clinical outcomes following extended criteria donor LTx surgery implementing a thoroughly protective allograft reperfusion strategy using CPB. METHODS: Thirty-nine consecutive adult patients who underwent bilateral LTx with elective CPB and protective allograft reperfusion were reviewed. Bilaterally implanted lungs were reperfused simultaneously, via slow CPB flow reduction and initial ventilation with 21% oxygen and nitric oxide, followed by a brief modified ultrafiltration. During weaning from CPB, mean pulmonary arterial pressure was strictly maintained at 10-15 mmHg by controlling CPB and pulmonary flow. The clinical outcomes in 23 patients who received lungs from extended criteria donors (ECD group) were elucidated and compared to 16 patients undergoing LTx from standard criteria donors (SCD group). RESULTS: No life-threatening deterioration was observed to graft functionality during the first 72 h after LTx in the ECD group; however, only one patient required post-transplant extracorporeal membrane oxygenation. In three of 23 ECD LTx patients (12%), surgical revision for bleeding was required. Survival outcomes for the ECD group were favorable, with 100% survival at 6-months, 87.0% at 1-year, and 80.7% at 5-years. Outcomes in the ECD group were comparable to those in the SCD group. CONCLUSIONS: Despite a certain extent of risk associated with full-dose heparinization, use of CPB does not undermine survival outcomes after ECD LTx surgery if protective allograft reperfusion is securely performed.