OBJECTIVES: To compare the renal outcomes in patients of unilateral renal cell carcinoma (RCC) with upper tract urothelial carcinoma (UTUC) following surgical resection of the tumor-bearing kidney, and to investigate the potential predictors in renal function decline. PATIENTS AND METHODS: In this retrospective cohort study, 319 RCC patients undergoing radical nephrectomy (RN) and 297 UTUC patients undergoing radical nephroureterectomy were recruited from a tertiary medical center between 2001 and 2010. Demographic data, co-morbidity, smoking habit, baseline estimated glomerular filtration rate (eGFR) calculated by chronic kidney disease-epidemiology equation, as well as tumor staging of RCC and UTUC, were recorded. The primary endpoint was serum creatinine doubling and/or end-stage renal disease (ESRD) necessitating long-term dialysis. Cox proportional hazard model and Fine and Gray's competing risk regression accounting for death were used to model renal outcome. RESULTS: UTUC patients had a higher incidence rate of renal function deterioration than RCC patients did (15.01 vs. 2.68 per 100 person-years, p<0.001). In Cox proportional hazard model and Fine and Gray's competing risk regression, UTUC was significantly associated with increased risk of creatinine doubling and/or ESRD necessitating dialysis (hazard ratio, 3.13; 95% confidence interval, 2.01-4.87) as compared to RCC following unilateral RN. Nevertheless, our study is observational in nature and cannot prove causality. CONCLUSIONS: UTUC per se is strongly associated with kidney disease progression as compared to RCC following unilateral nephrectomy. Further studies are needed to elucidate this association.