Background and Objective: Transitional cell carcinoma (TCC) of the renal collecting system traditionally has been managed by open nephroureterectomy with en bloc resection of a bladder cuff. However, for a select patient population with a solitary kidney or bilateral disease, the morbidity and mortality associated with chronic renal insufficiency and dialysis is deterring, In these situations, a more conservative approach such as antegrade percutaneous resection should be considered, The long-term disease-free outcome of percutaneous management in comparison with open nephroureterectomy has not been previously reported. We evaluated our experience with two surgical approaches to treat upper tract TCC: percutaneous resection and nephroureterectomy/nephrectomy to assess the clinical efficacy of these surgical modalities, Patients and Methods: We retrospectively identified 162 patients who had clinically localized TCC of the upper urinary tract. Records were reviewed to identify those with 13-year follow-up (N = 110) in respect to tumor grade, stage, disease-free status,length of cancer-specific survival, and overall survival. Statistical analysis of the results of open nephroureterectomy/nephrectomy (N = 60) and percutaneous resection (N = 50) was performed using Kaplan-Meier survival curves and Student's t-test. Results: All patients had disease in clinical stage Ta through T3. During a mean follow-up of 46.6 (range 6-150) months, grade 1 disease demonstrated little invasive potential. Of the disease-specific deaths, 60% (17/26) were of patients with grade 3 lesions, with a mean cancer survival period of 15.2 months after the initial procedure, Disease-specific survival rates after open and percutaneous approaches for grade 2 disease were 53.8 and 53.3 months, respectively (P > 0.05). Conclusions: Tumor grade appeared to be the most important prognostic indicator in patients with renal TCC regardless of the surgical approach. Grade 3 tumors were more aggressive, presenting in an advanced stage with invasion, and recurrences were usually associated with metastasis. In this population, nephroureterectomy is warranted if the patient is a surgical candidate. The percutaneous option for grade 1 or 2 disease may be extended beyond the population with solitary kidneys and a risk of chronic renal failure to be offered to healthy individuals with normal contralateral kidneys who are willing to abide by a strict and lengthy follow-up.