Background: Post-operative infection after radical cystectomy is a common complication. It is essential to identify modifiable risk factors that can predict post-operative infection to reduce the incidence of infection after radical cystectomy. We investigated the incidence of post-operative infection, associated pathogens, and risk factors for post-operative infection after radical cystectomy. Patients and Methods: Patients who underwent radical cystectomy for bladder cancer in a single urologic department from 2014 to 2016 were included. Age, gender, length of stay, body mass index (BMI), diabetes mellitus, hypertension, pre-operative estimated glomerular filtration rate, hydronephrosis, smoking status, neoadjuvant chemotherapy, pathologic tumor stage, pathologic nodal stage, types of urinary diversion, laparoscopic approach, operative time, and receipt of peri-operative blood transfusion were assessed to determine the association of these factors with the risk of infection within 30 days of radical cystectomy. Risk factors were assessed for correlation with any kind of infection and separately for urinary tract infection (UTI), blood infection/septic shock (BI), and surgical site infection (SSI). Pathogens were identified in all cases of infection. Results: A total of 134 patients were included in the analysis. Post-operative infection was diagnosed in 10.45%. Urinary tract infection, BI, and SSI were diagnosed in 3.73%, 4.48%, and 7.46%, respectively. Co-infections and mixed infection were diagnosed in 50% of patients with infection. Enterococcus was the most common pathogen. On multivariable analysis, age, BMI ≥30 kg/m2, and laparoscopic approach were associated with the risk of infection; odds ratios (ORs) were 1.27 (95% confidence interval [CI] 1.01–1.59), 13.07 (1.39–122.88), and 0.07 (0.01–0.78), respectively. Conclusion: One-tenth of patients undergoing radical cystectomy developed an infection within 30 days of surgery. Fifty percent of patients had co-infection with UTI, SSI, and/or BI and 50% of infections were polymicrobial. Increased BMI is the strongest factor associated independently with all types of infection. Therefore, obese patients should be encouraged to lose weight pre-operatively.