BACKGROUND AND AIMS: Based on endoscopic mucosal resection with ligation (EMR-L), we developed double band ligation-assisted endoscopic submucosal resection (ESR) for complete resection of small submucosal rectal neuroendocrine tumors (NETs). Both procedures use a multiband device to perform resection, with the only difference being that ESR adds an additional band to obtain deeper resection margin. This retrospective study aimed to validate its feasibility, safety, and effectiveness compared with EMR-L. METHODS: This retrospective study included consecutive patients with small (≤ 10 mm) suspected submucosal rectal NETs who underwent ESR (n=45) or EMR-L (n=26) between June 2018 and October 2023 at West China Hospital. En bloc resection rate, complete resection rate, procedure time, margin distance and adverse events were compared between two groups. RESULTS: En bloc resections were achieved in all patients. The complete resection rate of ESR was higher than EMR-L (100% vs. 88.5%, P=0.045). The vertical margin (VM) distance and lateral margin (LM) distance were significantly longer in ESR group than EMR-L group (VM distance 782.31 ± 359.45 μm vs. 363.84 ± 222.78 μm, P <
0.001
and LM distance 4205.75 ± 2167.43 μm vs. 3162.94 ± 1419.22 μm, P = 0.008, respectively). There were no significant differences in procedure time, adverse events, postprocedural hospital stay, or medical cost between two groups. In addition, there was no evidence of recurrence or metastasis during the follow-up. CONCLUSIONS: ESR appears to be safe and effective for complete resection of small submucosal rectal NETs. Larger, multicenter, prospective studies are needed to further assess this technique.