Study Need and Importance: Radical cystectomy (RC) for the management of muscle-invasive bladder cancer remains a morbid procedure with high rates of perioperative complications. 1,2 The role of preoperative immunonutritional supplementation (pre-INS) in improving post-RC outcomes is promising and needs further validation. 3e5 What We Found: We performed a retrospective review of 204 patients who underwent RC for bladder cancer at a single institution, comparing patients who received oral L-arginine-based pre-INS and those who did not. Preoperative features, postoperative complications, and readmission data were collected. Outcomes of interest included development of high-grade (Clavien-Dindo IIIeV) complications, readmission within 30 days, ileus, total parenteral nutrition requirement, postoperative infection, and length of stay (see table ). Multivariable logistic regression (MLoR) analysis was used to identify predictive factors for our outcomes. On MLoR, adjusting for age, gender, body mass index (BMI), Charlson comorbidity index, undergoing neoadjuvant chemotherapy, and operative features, pre-INS was a significant predictor of postoperative infection (Fisher p[0.02; OR[0.35), but not for other outcomes of interest. Limitations: Limitations of this study include its retrospective nature and its reliance on the presumption that all patients given pre-INS were fully compliant with taking the supplement. Furthermore, while preoperative albumin levels and BMI were not significantly different between the 2 patient groups, we were unable to directly assess patient perioperative nutritional status and sarcopenia, 2 increasingly recognized independent predictors of perioperative morbidity. Finally, enhanced recovery after surgery (ERAS) protocol implementation rates were high in both pre-INS and control groups (100% vs 72%, respectively), potentially confounding our findings, although pre-INS remained a significant predictor for postoperative infection after accounting for ERAS in our MLoR models. Interpretation for Patient Care: A short course of preoperative immunonutrition with an inexpensive Larginine-based supplement prior to RC is associated with significant reduction in postoperative infection, one of the most common complications of RC.