Purpose <p>This study evaluated oncological outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a high-volume tertiary center in Vietnam.</p> Methods <p>We performed a retrospective analysis of 134 consecutive patients with UTUC who underwent open or laparoscopic RNU at Cho Ray Hospital from 2017 to 2023. The primary outcome was overall survival (OS); secondary outcomes were metastasis-free survival (MFS) and the effect of adjuvant chemotherapy (AC) in patients with ≥pT2 and/or node-positive disease. Survival was assessed using Kaplan–Meier methods, and independent prognostic factors were identified with multivariate Cox regression.</p> Results <p>The median age was 65 years, and 60.4% were male. Advanced disease was common, with 78.4% of patients presenting with ≥pT2 tumors. Lymph node metastasis was identified in 9.7% of cases. OS rates at 1 and 3 years were 82.7% and 59.1%, respectively; corresponding MFS rates were 77.8% and 58.8%. Pathological T stage independently predicted both OS and MFS. Compared with pT1 disease, mortality risk increased markedly in pT2 (HR 5.95, 95% CI 1.31–27.04) and ≥pT3 (HR 19.20, 95% CI 4.29–85.48). AC provided a significant independent survival benefit, reducing the risk of death by more than half (HR 0.49, 95% CI 0.25–0.95) and decreasing metastatic risk (HR 0.25, 95% CI 0.11–0.55).</p> Conclusion <p>Pathological T stage remains a powerful independent prognostic factor after RNU. AC was associated with significant improvements in both survival and metastasis-free outcomes in advanced-stage UTUC. These findings offer robust real-world evidence from a major center in a low- to middle-income country and support current international guideline recommendations.</p>