Background: A prognostic model for patients with metastatic urothelial cell carcinoma (UCC) progressing following platinum-based therapy was constructed based on data from the phase 3 vinflunine trial. However, prognostic information for patients treated outside the setting of clinical trials and with variety of second-line regimens are limited. Methods: We gathered individual patient’s data from studies assessing second-line chemotherapy for metastatic UCC and analyzed the influence of factors of interest on overall survival (OS) through univariate and multivariate Cox-regression analysis. A prognostic model was constructed, and data of an independent series from a single institution was utilized for validation. Results: Data for 182 patients from seven studies were pooled. The second-line treatment was single agent in 22 (12%), platinum-based combination (nedaplatin or oxaliplatin) in 59 (33%), and non-platinum combination in 101 (55%). In multivariate analysis, Eastern Cooperative Oncology Group performance status ≥1, Hb<10, and metastatic patterns other than LN only metastasis emerged as independent adverse factors. Patients with all three factors (poor risk), 1-2 factors (intermediate risk), and 0 factors (Good risk) had median OS of 3.1, 8.8, and 16.5 months respectively, p< 0.0001. The corresponding median OS for the validation series (n = 44) were 3.3, 8.1, and 13.3 months, p = 0.023. Platinum – based regimens were associated with OS benefit compared to other combination regimens and to single agents, such benefit was retained when this factor was included in multivariate analysis (HR: 3.1, 95% CI: 1.82- 4.98, p< 0.0001). In addition, freedom of progression at 6 months from initiation of second- line therapy correlated with improved survival compared to progression within 6 months; median OS 13.9 and 6.6 months respectively, p< 0.0001. Conclusions: We proposed and validated a prognostic model for patients with metastatic UCC who are eligible for second-line therapy. The proposed model may prove helpful for risk-stratification. Furthermore, our data suggest that testing second- line platinum-based regimens in randomized trials is warranted.