Perioperative blood transfusion adversely affects prognosis of patients with stage I non-small-cell lung cancer. It has been speculated that blood transfusion might adversely affect prognosis in cancer patients by immunosuppression. To avoid the confounding affect of advanced disease, we tested this hypothesis in 117 patients with stage I non-small-cell lung cancer. Mean and median follow-up were 49.7 months and 47 months, respectively. Patients who died during the postoperative period were not included. Perioperative transfusion was defined as administration of whole blood or packed cells within 30 days of operation. The overall cumulative 5-year disease-free survival rate was 67%. In patients with transfusion, it was 53% and in patients without transfusion it was 81% (p = 0.0055). A multivariate analysis was performed that included patient age, race, sex, cell type, extent of operation (pneumonectomy versus lobectomy/segmentectomy), operative blood loss, admission hematocrit, discharge hematocrit, and the presence or absence of perioperative transfusion. The only variable that significantly correlated with 5-year disease-free survival was the presence or absence of perioperative transfusion (p = 0.0278), and this effect was not related to the number of transfusions. Retrospective analysis of long-term results of patients surviving curative operation for stage I lung cancer shows that any perioperative transfusion significantly worsens the patient's prognosis and suggests very strongly that this association is due to an adverse effect of the transfusion rather than the transfusion serving as a marker for another risk factor. 