Purpose To assess the incidence, risk factors, and clinical outcomes associated with (Clostridioides difficile infection) CDI following urological surgery, which is the leading cause of nosocomial diarrhea and a growing public health burden. Methods We queried the National Surgical Quality Improvement Program (NSQIP) to identify patients undergoing urological surgery in 2015-2016. We evaluated the 30-day incidence and factors associated with postoperative CDI and 30-day hospital readmission and length of stay as secondary outcomes. Among the subset of patients undergoing radical cystectomy with urinary diversion (surgery with highest CDI incidence) we used multivariable logistic regression analysis to evaluate independent clinical and demographic factors associated with postoperative CDI. Results We identified 98,463 patients during the study period. The overall 30-day incidence of CDI was 0.31%, but varied considerably across surgery type. The risk of CDI was greatest following radical cystectomy with urinary diversion (2.72%) compared to all other urologic procedures (0.19%) and was associated with increased risk of hospital readmission (p < 0.0001), re-operation (p < 0.0001), and longer mean length of stay (p < 0.0001) in this cohort. Among patients undergoing radical cystectomy with urinary diversion, multivariable logistic regression revealed that preoperative renal failure (OR: 5.30, 95% CI 1.13-24.9, p = 0.035) and blood loss requiring transfusion (OR: 1.67, 95% CI 1.15-2.44, p = 0.0075) were independently associated with CDI. Conclusions In a nationally representative cohort, the incidence of CDI was low but varied substantially across surgery types. CDI was most common following radical cystectomy and associated with potentially modifiable factors such as blood transfusion and significantly longer length of stay.