Endoluminal clip closure of small perforations of the colon is possible. It is unclear whether large perforations of the colon can be closed with clips deployed through a colonoscope.To evaluate the technical feasibility and outcome of endoluminal closure of large perforations of the colon with clips.Pilot study.Eight pigs.Endoluminal clip closure of large perforations of the colon.Technical feasibility of endoluminal closure was evaluated in 8 animals. A dye leak test was performed to evaluate quality of endoluminal sealing immediately after closure and 2 weeks after closure. The animals in the survival group were monitored daily for 2 weeks for sepsis and peritonitis. Necropsy was done on day 14 to check for fecal peritonitis, wound dehiscence, and histological healing of perforation.Endoscopic closure of colon perforation was successful in 6 of 8 animals; in 2 animals closure was unsuccessful due to prolapse of adjacent viscera into the colon (n = 1) and severe bleeding that obscured the view (n = 1). There was a leak-proof sealing of the perforation site in 2 animals tested immediately and in all the animals tested (n = 3) 2 weeks after closure. All 4 animals in the survival group recovered well, without any sepsis or peritonitis. Necropsy did not reveal fecal peritonitis or pericolonic abscess formation. The perforation site demonstrated a thin scar and there was histological healing.Endoluminal application of clips is successful in the closure of a large perforation of the colon in a porcine model.