© 2018 Elsevier Inc. Upper tract urothelial carcinoma is a rare disease and most of the treatment guidelines are extrapolated from urothelial carcinoma of the bladder. In this retrospective study, we were able to identify baseline features, treatment patterns, and prognostic factors, which could be used in risk stratification, management decision-making, and disease-specific clinical trial design. Background: Upper tract urothelial carcinoma (UTUC) accounts for approximately 5% of all urothelial cancers. Because of similarities in morphology and histology between UTUC and urothelial carcinoma of the bladder, most treatment guidelines used for UTUC are extrapolated from the urothelial bladder carcinoma setting. With the emergence of new treatment modalities, such as immunotherapy, UTUC-specific prognostic and predictive models are needed. Patients and Methods: A retrospective study of 454 UTUC patients who received surgery at Cleveland Clinic (1995-2014) was conducted. Univariable and multivariable analysis (MVA) was used to identify independent predictors of progression-free survival (PFS) and overall survival (OS). Results: Two hundred eighty-six patients with invasive UTUC were identified with pT1, pT2, pT3, and pT4 in 93 (33%), 51 (18%), 126 (44%), and 16 (6%), respectively. Most patients (76%) had laparoscopic nephroureterectomy, 14% had positive invasive surgical margins, and 22% had multifocal tumors. All patients had urothelial carcinoma as primary histology, 93 of 183 (51%) with available follow-up data had disease recurrence. Estimated median PFS was 17.2 months (95% confidence interval [CI], 13.1-39.3). In MVA, pT stage (P =.0005), positive margins (P =.04), and age older than 70 years (P =.002) independently correlated with PFS. Overall, 101 patients (37%) of 272 patients with available data died with estimated median OS of 64.5 months (95% CI, 39.3-107.4); median follow-up was 39.5 (range, 0.3-186) months in patients alive and recurrence-free at last follow-up. In MVA, lymphovascular invasion (P =.005), tumor size (P =.0005), age (P =.005), and pT stage (P =.03) independently predicted OS. Using these factors, 3 prognostic groups for PFS and 2 for OS were identified. Conclusion: Clinical-pathological parameters can be prognostic in UTUC and might inform clinical trial design and decision-making.