Objective: To report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large study sample. Materials and methods: This was a nationwide multicenter registry-based cohort study of all patients with upper urinary tract urothelial neoplasia in Denmark found to be eligible for nephroureterectomy between April 2004 and April 2017 (N = 1384). Primary endpoints were intravesical recurrence-free survival and overall survival. Survival probabilities were estimated with Kaplan–Meier and the log-rank test to compare survival curves. Association with clinical outcomes was studied using univariate and multivariate Cox proportional hazards. Results: Intravesical recurrence-free survival was 72% [95% confidence interval (CI) 69–75%] at 5 years and 70% (95% CI 67–73%) at 10 years. Patients with muscle-invasive disease had a significantly lower rate of intravesical recurrence [hazard ratio (HR) = 0.46, p < 0.0001] and patients with high-grade tumors had a significantly higher rate of incident intravesical recurrence compared to low-grade tumors (HR = 1.65, p = 0.001). The overall survival was 76% (95% CI 74–79%) at 5 years and 64% (95% CI 60–70%) at 10 years. Patients with higher age (p = 0.008) and muscle-invasive disease (p < 0.0001) had worse overall survival. When comparing surgical approaches, laparoscopic nephroureterectomy versus open nephroureterectomy did not differ in intravesical recurrence-free survival but was associated with shorter postoperative hospital stay (p < 0.0001) and better overall survival (p = 0.02). Conclusions: We report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large sample and give insights into predictive factors with significant impact.