INTRODUCTION: This study aims to assess the influence of different prognostic factors on survival of upper tract urothelial carcinoma (UTUC) managed by nephroureterectomy and to investigate whether these factors have an independent prognostic significance. MATERIALS AND METHODS: A retrospective review of institutional databases from two teaching hospitals identified 269 consecutive patients with UTUC managed with nephroureterctomy between 1985 and 2005. Mean follow up was 80.6 months (median 70.3 months). Follow up was completed until January 2009. Tumor location and other clinicopathological variables were analyzed regarding survival. Data accrued included age, gender, tumor characteristics (pT stage, grade, lymph node status), tumor location, use of chemotherapy and period of diagnosis. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the tumor. RESULTS: Five year and 10 year overall survival estimates for this cohort were 71.3% and 40.0% respectively. According to tumor location, survival was 73.6% and 47.0% for the renal pelvis versus 67.8% and 32.3% for the ureter, respectively (log rank test: p = 0.027). In multivariate analysis, among the clinicopathological variables, T stage was the most significant prognostic factor (p < 0.001). Nodal involvement (p = 0,005), high grade (p < 0.001), first period of diagnosis (p < 0.001) and ureteral tumor location (p = 0.003) were significantly associated with lower survival rates. Prognosis of UTUC improved over time: survival was significantly better during the last period of diagnosis (2001-2005) (p < 0.002). CONCLUSIONS: Tumor location and diagnostic period should be considered as an independent prognostic factor for upper tract transitional cell carcinoma.