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Our results indicate that renin-angiotensin system inhibitors significantly reduced the risk of recurrence and cancer-specific mortality after radical surgery for urothelial carcinoma of the upper urinary tract. Renin-angiotensin system inhibitors may therefore improve oncological outcomes.Renin-angiotensin system (RAS) inhibitors are effective for treating patients with cancer. The present study evaluated the impact of RAS inhibitors, including angiotensin-2 converting enzyme inhibitors and angiotensin 2 receptor blockers, after patients underwent radical surgery for upper urinary tract urothelial carcinoma (UTUC).This retrospective study included 312 patients with nonmetastatic UTUC who underwent radical surgery. The oncological outcomes of patients treated or not treated with RAS inhibitors following surgery were evaluated. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan-Meier method and Cox regression analysis.The median follow-up duration after radical surgery was 44.7 months. The 5-year RFS, CSS, and OS rates of patients who did or did not receive RAS inhibitors were 82.3% versus 68.9% (P = .018), 88.9% versus 71.8% (P = .0044), and 68.7% versus 61.8% (P = .047), respectively. Multivariable analyses revealed that the use of RAS inhibitors was an independent prognostic factor for RFS, CSS, and OS (hazard ratio [HR] 0.48, P = .013; HR 0.31, P = .002; and HR 0.52, P = .01, respectively). Moreover, patients treated with RAS inhibitors versus untreated patients had better 5-year RFS compared with those in the pT2 and < pN1 subgroups (pT2: 100.0% vs. 62.2%, P = .014 and < pN1: 87.2% vs. 74.7%, P = .034).RAS inhibitors significantly improved RFS, CSS, and OS of patients with UTUC who underwent radical surgery. These agents may be particularly beneficial for patients with stage pT2 or < pN1 disease.