INTRODUCTION: Infectious complications are common after radical cystectomy (RC), and allogeneic blood transfusions may increase infection risk by an immunosuppressive effect. While it has been suggested that perioperative blood transfusion (PBT) may be associated with adverse oncologic outcomes after RC, no large analyses have assessed whether PBT increases the risk of perioperative infection after RC. MATERIALS AND METHODS: We used the Nationwide Inpatient Sample (1998 to 2011) to study the rate of PBT during RC for bladder cancer and identify infectious complications. We compared rates of infectious complications in patients who did and did not receive PBT and developed a multivariable model to assess the independent risk of infectious complication associated with PBT controlling for age, year of surgery, obesity, chronic kidney disease, comorbidity score, and type of urinary diversion. RESULTS: We identified 126,454 RCs performed during the study period. A total of 34,203 (27%) received a PBT. The use of PBT increased over the study period, from 18.4% in 1998 to 31.6% in 2011 (p < 0.0001). Patients who received a PBT had an increased risk of perioperative infectious complications [36.7% versus 27.7%, unadjusted OR (95% CI) = 1.51 (1.43-1.60), p < 0.0001]. After adjusting for potential confounders, PBT remained an independent predictor of infectious complications [adjusted OR (95% CI) = 1.46 (1.38-1.55), p < 0.0001]. CONCLUSIONS: This analysis provides strong observational evidence that PBT is associated with an increased risk of perioperative infectious complications, which may be secondary to transfusion-related immunomodulation. Urologists should aggressively pursue blood conservation strategies and adhere to evidence-based restrictive transfusion thresholds, particularly given the rising rate of PBT.