Background: Radical cystectomy (RC) still poses a significant risk for mortality and morbidity. Objectives: We compared in-hospital outcomes after RC in the United States and Germany using population-based data. Methods: We compared data from the US Nationwide Inpatient Sample to the German hospital billing database. Mortality and transfusion during hospital stay and length of stay (LOS) were evaluated. Results: In all, 17,711 (the United States) and 60,447 (Germany) cases were included. The share of robot-assisted RC increased to 20.5% in the United States vs. 2.3% in Germany (p < 0.001). In-hospital mortality was 1.9% (the United States) vs. 4.6% (Germany), transfusion rates were 34.2% (the United States) vs. 58.7% (Germany), and LOS was 10.7 (the United States) vs. 25.1 days (Germany; all p < 0.001). On multivariate analysis, higher patient age and lower annual hospital caseload were associated with increased mortality and longer LOS. Minimal-invasive surgery was associated with less blood transfusion and shorter LOS in the United States vs. hospital caseload and choice of urinary diversion in Germany. Conclusions: Healthcare systems might exert a relevant impact on outcomes of oncologic surgery. Increased in-hospital mortality rates in Germany seem to be partly explained by much longer LOS compared to those in the United States. Annual caseload seems to be influential on in-hospital outcomes raising the question of centralization of RC.