Background: African-American race appears to be associated with higher stages of urothelial carcinoma of the bladder (UCB) at presentation and poorer survival. However, the independent effect of African-American race on objective tumor recurrence after radical cystectomy (RC) after controlling for clinical and pathologic variables is unknown. Patients and Methods: The data from consecutive patients with UCB who underwent RC with curative intent at a single institution (University of Alabama, Birmingham) from 2001 to 2012 with or without perioperative chemotherapy or chemoradiation were reviewed. The patient demographics, risk factors, clinical course, pathologic characteristics, and long-term outcomes were collected. Descriptive statistics were performed. Cox regression analysis was performed for key clinical, demographic, and pathologic variables, including race, stratified as African American versus white. Results: A total of 215 patients, 163 men (76%) and 52 women (24%), with a mean age at RC of 65.6 years, were identified and reviewed. A total of 186 patients (87%) were white and 28 (13%) were African American. The median follow-up period after RC was 17.6 months. On conventional multivariate analysis, African-American race nearly attained statistical significance (hazard ratio [HR], 2.48; 95% confidence interval [CI], 0.98-6.29; P =.055). In a stepwise regression model, race was significantly associated with tumor recurrence (HR, 3.11; 95% CI, 1.2-7.4; P <.011). Conclusion: African-American race appears to be independently associated with a greater risk of tumor recurrence after RC for UCB. The effect of host genetics on tumor biology needs to be characterized at the genomic level to develop precision medicine.