Purpose The natural history and risk of disease progression in patients with positive urine cytology after radical cystectomy for urothelial carcinoma has not been adequately elucidated. Materials and Methods An institutional review board approved, retrospective review in patients undergoing radical cystectomy was performed to identify those with positive urinary cytology after radical cystectomy. Cox proportional hazards regression was used to determine factors associated with positive cytology after radical cystectomy and upper tract recurrence after positive cytology. Survival curves and probabilities were examined by Kaplan-Meier analysis. Results A total of 101 patients with at least a single positive urinary cytology result after radical cystectomy were identified. Ureteral involvement in the radical cystectomy specimen was significantly associated with subsequent positive cytology. At the first positive urinary cytology only 9 of 101 patients (9%) had documented urothelial recurrence but eventually 57 of 101 had radiographic evidence of urothelial recurrence. Median freedom from radiological evidence of urothelial recurrence after positive cytology was 2.1 years and ureteral involvement was associated with a higher likelihood of urothelial recurrence. Despite surgical and chemotherapeutic interventions median survival after urothelial recurrence was 2.1 years. Conclusions Urine cytology may have a valuable role for detecting upper tract recurrence after radical cystectomy. Most patients with positive cytology after radical cystectomy eventually have radiological evidence of urothelial recurrence. These data may help clarify natural history in patients with positive cytology after radical cystectomy. Additionally, these data indicate the need for diligent evaluation for recurrent disease and potentially the role of early adjuvant therapy in patients with positive cytology after radical cystectomy.