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A b s t r a c tIntroduction: Owing to the development of the laparoendoscopic single-site (LESS) procedure, transumbilical LESS nephroureterectomy (LESS-NU) has become a new approach for treating upper tract urothelial carcinoma. Aim: The aim of this study is to introduce a modified LESS-NU procedure with bladder cuff excision for treating upper tract urothelial carcinoma (UTUC). We compared its clinical efficacy and postoperative outcomes in terms of follow-up time with traditional retroperitoneal laparoscopic nephroureterectomy (RL-NU). Material and methods: From May 2014 to May 2019, we performed nephroureterectomy on 42 patients using the retroperitoneal approach and a modified LESS approach. A retrospective analysis was conducted for the evaluation of the clinical and postoperative outcomes between the two groups. Results: The study included 25 LESS-NU and 17 RL-NU patients. All the procedures were completed successfully. The LESS-NU group had a significantly shorter mean operative time than the 236.18 min, p = 0.005). The differences in skin incision length (2.88 cm, 8.94 cm, p < 0.001) and oral analgesic dose (n = 1.12, n = 2.75, p < 0.001) between LESS-NU and RL-NU were statistically significant. Conclusions: Modified LESS-NU is a feasible and safe procedure. Compared with the retroperitoneal laparoscopic approach, the single-site approach did not alter the patients' position. LESS-NU is a better procedure for treating UTUC than RL-NU in terms of cosmetic result and postoperative pain.