SUBJECTS: The aim of this study is to compare the efficacy and safety of en bloc bladder tumor-endoscopic submucosal dissection (BT-ESD) and conventional transurethral resection of BT (TURBT) in nonmuscle invasive bladder cancer (NMIBC) patients. METHODS: A retrospective cohort study was carried out in Shaanxi Provincial People's Hospital. A total of 193 eligible NMIBC (Ta/T1) patients were enrolled in this study (95 cases in BT-ESD group and 98 cases in TURBT group), between November 2013 and January 2017. The operation time, blood loss, postoperative bladder irrigation time, catheter indwelling time, hospital stay time, and complications were compared. Data were presented as median (range). Chi-squared or rank-sum test, two-way ANOVA, and Mantel-Cox (Log-Rank) test were performed using statistical software. A threshold of P < 0.05 was defined as statistically significant. RESULTS: The average operation time in the BT-ESD group was longer than that of in the TURBT group (40.0 [5.0, 100.0] min vs. 19.5 [3.0, 55.5] min); however, no significant longer operating time (P < 0.05) were observed in the smaller tumor (0 cm-3 cm). The postoperative bladder irrigation time, catheter indwelling time, and hospital stay in BT-ESD group were significantly shorter than that of in TURBT group (9.0 [5.0, 18.0] h, 2.5 [1.0, 4.0] d and 3.5 [2.0, 5.0] d for BT-ESD; 18.0 [12.0, 48.0] h, 3.5 [2.0, 7.0] d, and 4.5 [3.0, 8.0] d for TURBT). In addition, the BT-ESD group showed the decreased overall incidence of complications (2.1% vs. 9.2%). The univariate and multivariate analyses indicated an association between surgical option and tumor recurrence (hazard ratio = 5.624, odds ratio = 95% confidence interval = 1.582-19.991), Kaplan-Meir analysis showed significant difference in recurrence-free survival (RFS) (94.7% for ESD group vs. 78.4% for TURBT group) at 33 months. CONCLUSIONS: The application of the HybridKnife lead to a decrease in complications and RFS rate, which was a more safe and effective approach for NMIBC than conventional TURBT.