Objective To compare the oncologic outcomes of patients with upper tract urothelial carcinoma undergoing nephroureterectomy (NU) with and without prior ureteroscopy (URS). Methods We reviewed records of all patients with no prior history of bladder cancer who underwent NU at our institution (n = 201). We compared patients who underwent URS before NU with patients who proceeded directly to NU based on imaging alone. After excluding patients undergoing URS with therapeutic intent, we used multivariable Cox proportional hazards models, adjusting for tumor characteristics with cancer-specific survival (CSS), intravesical recurrence-free survival, metastasis-free survival (MFS), and overall survival (OS) as end points. This study received institutional review board approval. Results A total of 144 (72%) patients underwent URS before NU, and 57 (28%) patients proceeded directly to NU. The median follow-up time for survivors was 5.4 years from diagnosis. The performance of diagnostic URS before NU was significantly associated with IR (hazard ratio 2.58; 95% CI 1.47, 4.54; P = .001), although it was not associated with CSS, MFS, or OS. The adjusted intravesical recurrence-free survival probability 3 years after diagnosis is 71% and 42% for patients who did not and did receive URS before NU, respectively (adjusted risk difference 30%; 95% CI 13%, 47%). Conclusion We did not find evidence that URS adversely impacts disease progression and survival in patients with upper tract urothelial carcinoma. Although patients are at higher risk for IR after NU when they have undergone prior diagnostic URS, their CSS, MFS, and OS are not significantly affected.