Abstract Background The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood. Objective To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC). Design, setting, and participants Data from 8102 patients treated with RC (6497 men 80% and 1605 women 20%) for UCB between 1971 and 2012 were analyzed. Outcome measurements and statistical analysis Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI). Results and limitations Female patients were older at the time of RC ( p = 0.033) and had higher rates of pathologic stage T3/T4 disease ( p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR ( p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM ( p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05). Conclusions We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.