Background <p>This study aimed to compare radical nephroureterectomy (RNU) and distal ureterectomy (DU) in managing high-risk distal ureteral urothelial carcinoma (UC), focusing on renal function, adjuvant chemotherapy (AC), and oncologic outcomes.</p> Methods <p>A retrospective analysis was conducted on 758 patients initially identified with high-risk distal ureteral cancer treated from 2008 to 2021 at two national centers in Beijing and Guangzhou, China. After selection, 554 patients were included: 371 in the RNU group and 183 in the DU group. Propensity score matching (PSM) was applied, resulting in 176 patients in each group. Primary outcomes included intravesical recurrence-free survival (IVRFS), extravesical recurrence-free survival (EVRFS), overall survival (OS), and cancer-specific survival (CSS). Secondary outcomes assessed associations between eGFR, AC, and survival.</p> Results <p>After PSM, RNU provided better recurrence control, showing significantly higher IVRFS, particularly in T1/N- and low-grade cases, and in patients with eGFR ≥ 50&#xa0;mL/min/1.73 m². DU, however, demonstrated superior renal function preservation across all postoperative time points (<i>p</i> &lt; 0.01). Higher postoperative eGFR was associated with increased AC administration and improved OS (<i>p</i> = 0.0010) and CSS (<i>p</i> = 0.0003). In advanced-stage (T2-4/N +) tumors, AC was linked to better OS (<i>p</i> = 0.0399) and a trend toward improved CSS. Additionally, variant histology (VH) and positive surgical margins were confirmed as significant negative prognostic factors for survival.</p> Conclusions <p>RNU is preferred for early-stage, low-grade cases due to its superior recurrence control, particularly for IVRFS. DU offers comparable outcomes in advanced-stage or high-grade cases, with the added advantage of renal preservation, supporting chemotherapy eligibility. Individualized treatment strategies based on patient-specific factors remain essential for optimizing outcomes in high-risk distal ureteral UC.</p>