Background: Limited data exists to support the benefit from second-line chemotherapy in patients with metastatic urothelial carcinoma. Factors that predict survival following progression after first-line platinum-based regimens in patients treated outside clinical trials are not clear. This study intends to evaluate different prognostic factors and the impact of second-line chemotherapy on survival.Methods: We retrospectively reviewed patients with metastatic urothelial carcinoma who experienced disease progression following first-line platinum-based regimens for metastases. These patients received treatment and follow up visits at a single institution. The effect of demographic, disease characteristics, and second-line therapy on overall survival was examined through univariate and multivariate cox-regression analyses.Results: There were 64 patients included. A total of 27 (42%) patients did not receive second-line chemotherapy because of poor Eastern Cooperative Oncology Group performance status, 20 (31%) received combination chemotherapy (platinum-based in 17), and 17 (27%) received a single agent chemotherapy. The median overall survival from the date of documented progression after first-line therapy was 5.0 months. In multivariate analysis, a correlation existed between poor overall survival and performance status of ≥1 (HR: 5.74, 95% CI: 1.4- 45.57, P=0.036), no second-line chemotherapy (HR: 2.72, 95% CI: 1.39-5.31, P=0.003), and ≥2 metastatic sites (HR: 5.19, 95% CI: 1.74-15.44, P<0.001).Conclusion: A significant proportion of patients with metastatic urothelial carcinoma were not eligible for second-line chemotherapy because of poor performance status. Use of second-line chemotherapy, Eastern Cooperative Oncology Group performance status, and number of metastatic sites were important determinants of survival.