OBJECTIVE: Pulmonary dysfunction is common in transfused patients recovering from heart surgery. Plasma transfusion from female donors has been linked with rare catastrophic lung injury, but its relationship with outcome after cardiac surgery is poorly understood. We examined whether plasma donor gender is related to postcardiac surgery pulmonary dysfunction and death or prolonged hospitalization. METHODS: In this retrospective case-control study, cardiac surgery candidates who received plasma perioperatively from only female donors were compared with male-only recipients who were matched for the number of units transfused and surgery date. RESULTS: In a dataset of 2157 recipients, there were no blood bank-reported complications, but escalating plasma transfusion was associated with increased 30-day mortality (odds ratio, 1.52 per unit; P = .0001). From the 1069 recipients receiving plasma exclusively from female or male donors, 390 matched pairs were identified. Recipients of female compared with male donor plasma had a lower incidence of pulmonary dysfunction (5.9% vs 10.8%; P = .01) and death or hospitalization more than 10 days (9% vs 16.4%; P = .002) but similar long-term survivals. CONCLUSIONS: Escalating plasma transfusion was associated with 30-day mortality, but female donor plasma recipients had less pulmonary dysfunction and fewer poor outcomes compared with male-only recipients. Although our retrospective study findings neither support nor refute a strategic policy to exclude female donor plasma to reduce catastrophic transfusion-related acute lung injury, they raise concern that such a policy may have unanticipated effects on outcome in patients undergoing cardiac surgery and highlight a need for additional studies in this and other patient groups.