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Background Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection. Methods We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n = 59) who underwent lung transplantation off‐pump (n = 26), with cardiopulmonary bypass (CPB; n = 18), or with extracorporeal membrane oxygenation (ECMO; n = 15). Peripheral blood was collected from patients at baseline and at 6 and 72 h after reperfusion. To adjust for clinical differences between groups, we utilized a linear mixed model with overlap weighting. Results PGD3 was present at 48 or 72 h after reperfusion in 7.7% (2/26) of off‐pump cases, 20.0% (3/15) of ECMO cases, and 38.9% (7/18) of CPB cases (p = 0.04). The ECMO and CPB groups had greater reperfusion‐induced increases in MIP‐1B, IL‐6, IL‐8, IL‐9, IL1‐ra, TNF‐alpha, RANTES, eotaxin, IP‐10, and MCP‐1 levels than the off‐pump group. Cytokine expression profiles after reperfusion were not significantly different between ECMO and CPB groups. Conclusion Our data suggest that, compared with an off‐pump approach, the intraoperative use of ECMO or CPB during lung transplantation is associated with greater reperfusion‐induced cytokine release and graft injury.