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Retrospective cohort study.The objective of this study is to compare the incidence of infection in patients who do and do not receive blood transfusions in major deformity surgery (>8 levels).Postoperative infections increase morbidity and mortality rates in spine surgery and generate additional costs for the health care system. It has been proposed that blood transfusions increase the risk of wound infection, urinary tract infection, pneumonia, and sepsis.A total of 56 patients met the study criteria, receiving spine surgery involving the fusion of 8 levels or more. Patient-specific characteristics, starting and ending hematocrits, number of units transfused and infections including urinary tract infection, wound infection, pneumonia, and sepsis were documented. Differences in infection risk between those who did and did not undergo a transfusion and their 95% confidence intervals were calculated.Groups were similar with respect to baseline and surgical characteristics except for smoking status, operative time, estimated blood loss, and ending hematocrit. The overall infection rate was greater in patients who underwent transfusion than those who did not (36% vs. 10%; P=0.03). Wound infections (n=5) were only observed in those who underwent a transfusion. Smokers were more likely to receive a transfusion and more likely to experience infection. A stratified analysis demonstrated an increased risk of infection associated with transfusion; however, the risk was greater in smokers, suggesting the effect of transfusion on infection could be modified by smoking. Patients undergoing transfusion experienced a significantly longer hospital stay (P=0.01).Allogeneic red blood cell transfusion in major spine surgery could be a risk factor for postoperative infection. This increased risk seems to be magnified in those who smoke. Further studies are warranted, and risks of blood loss and transfusion-related complications in smokers also potentially merit exploration.Level 3.