Purpose: To evaluate the effect of lymphadenectomy (LND) in conjunction with nephroureterectomy on cancer-specific mortality (CSM) and overall survival (OS) for patients with muscle-invasive UTUC. Methods: A retrospective, multicenter study of patients with UTUC, clinical stage N0M0, who underwent nephroureterectomy between January 2008 and December 2014 was conducted. Outcome measures were OS and CSM. Results: In total, 298 patients underwent robot-assisted or laparoscopic radical nephroureterectomy with a final histological diagnosis of UTUC. LND was performed in 46 (15.4%). One hundred and seventy-two patients (62%) had non-muscle-invasive disease (NMID); 105 patients (38%) had muscle-invasive disease (MID). Median time of follow-up was 43.5 months (95% CI 36.0–47.2). For patients with MID, the 5-year cumulative incidence of all-cause mortality and CSM was 73.5% (95% CI 60.4–86.6) and 52.4% (95% CI 38.9–65.9), respectively (p < 0.0001). There was no significant difference in OS between patients with N1 and patients with N0 disease (p = 0.53). The 5-year OS rates were 30.5% (95% CI 6.6–54.4) and 25.7% (95% CI 10.9–40.5), respectively. This study is limited by its retrospective nature. There may also have been bias in the selection of patients undergoing LND. Conclusions: Five-year OS and CSM are comparable between patients with N1 and N0 MID. This evidence may support the use of the LND procedure in patients with muscle-invasive UTUC.