Background and aims <p>The effectiveness of defect closure in preventing postoperative complications in rectal lesions exceeding 30 mm in size following endoscopic submucosal dissection (ESD) remains uncertain; this study aimed to assess the effectiveness of defect closure in reducing postoperative complications after ESD in patients with large rectal neoplasms.</p> Methods <p>A retrospective review was conducted on consecutive patients with large rectal neoplasms who underwent ESD at our center from January 2013 to December 2024. Patients were divided into two groups: the closure group and the non-closure group. Propensity score matching (PSM) was used to minimize selection bias. The study compared adverse events, postoperative fever, and postoperative hospital stay between the two matched groups.</p> Results <p>A total of 215 patients were enrolled in the study and included in the analysis. The baseline characteristics of the 83 matched patient pairs were comparable after PSM. The incidence of adverse events was significantly lower in the closure group than in the non-closure group (1.2% vs. 9.6%, P = 0.040). While no statistically significant differences were observed between the two groups in terms of postoperative fever and prolonged postoperative hospital stay, the rates were lower in the closure group compared to the non-closure group (9.6% vs. 10.8%, <i>P</i> = 0.798; 22.9% vs. 33.7%, <i>P</i> = 0.121, respectively). Moreover, defect closure was independently associated with a reduced risk of delayed bleeding (OR, 0.181; 95% CI, 0.035–0.932; <i>P</i> = 0.041).</p> Conclusion <p>Defect closure after ESD decreased the adverse events in patients with large rectal neoplasms. Moreover, defect closure was independently associated with a reduced risk of delayed bleeding. Future prospective studies with larger samples are needed to provide more definitive guidance for clinical practice.</p> Graphical Abstract <p></p>