Background: Limited data exists to support the benefit from second-linechemotherapy in patients with metastatic urothelial carcinoma. Factors that predictsurvival following progression after first-line platinum-based regimens in patientstreated outside clinical trials are not clear. This study intends to evaluate differentprognostic factors and the impact of second-line chemotherapy on survival. Methods: We retrospectively reviewed patients with metastatic urothelial carcinomawho experienced disease progression following first-line platinum-based regimens formetastases. These patients received treatment and follow up visits at a single institution. The effect of demographic, disease characteristics, and second-line therapy on overallsurvival was examined through univariate and multivariate cox-regression analyses. Results: There were 64 patients included. A total of 27 (42%) patients did not receivesecond-line chemotherapy because of poor Eastern Cooperative Oncology Groupperformance status, 20 (31%) received combination chemotherapy (platinum-based in17), and 17 (27%) received a single agent chemotherapy. The median overall survivalfrom the date of documented progression after first-line therapy was 5. 0 months. Inmultivariate analysis, a correlation existed between poor overall survival and performancestatus 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 carcinomawere not eligible for second-line chemotherapy because of poor performance status. Use of second-line chemotherapy, Eastern Cooperative Oncology Group performancestatus, and number of metastatic sites were important determinants of survival.