BACKGROUND Endoscopic sphincterotomy (EST) can destroy sphincter of Oddi (SO) structure and function. The purpose of this study was to assess the feasibility of endoscopic endoclip papilloplasty (EEPP) in restoring SO function after EST. METHODS Seven 26-week-old domestic pigs were divided into control and EEPP groups. Necropsy and haematoxylin-eosin staining plus anti-α-smooth muscle actin (α-SMA) staining of papilla and sphincter of Oddi manometry (SOM) were conducted in animals at three independent time points. RESULTS EST and EEPP were safely performed in all 7 pigs without serious adverse events. For primary outcome, compared to the controls, EEPP generated smaller dilation and less inflammation. Fibrous repair of the papilla was observed at 24 weeks after EEPP. For secondary outcome, in the control group, SO basal pressure (17.25 ± 18.14 to 5.50 ± 0.71 mmHg), SO contraction amplitude (46.00 ± 19.20 to 34.50 ± 48.79 mmHg), peak (4.50 ± 4.04 to 1.50 ± 2.12) and frequency (3.05 ± 3.29 to 1.41 ± 2.19/min) were reduced after EST. Further reductions to almost 0 of these SOM parameters were observed 3 weeks later, including common bile duct pressure and SO contraction period. In contrast, in the EEPP group, these manometric data were recovered to pre-EST levels, including CBD pressure (11.5 ± 7.31 vs 11 ± 2.16 mmHg), SO pressure (17.50 ± 17.75 vs 18.20 ± 21.39 mmHg) and SO contraction amplitude (53.67 ± 21.54 vs 60.00 ± 36.08 mmHg). However, no significant differences were observed between control and EEPP groups by Student t test. CONCLUSIONS In this porcine study, EEPP accelerated and improved papillary healing after EST, further preserved SO function.