Iatrogenic perforation of the colon during interventional endoscopic procedures, e.g., mucosectomy, is a problematic complication, as safe treatment often requires surgical repair. Iatrogenic perforation of the colon is indeed a rare complication; however, given the increasing case numbers in interventional endoscopy it is of considerable practical relevance. The closure of perforations can be achieved with conventional endoscopic clips; however, these working channel based clips are often too small to close a perforation securely. Therefore, we have developed a novel endoscopic clipping system that can be attached to the tip of the endoscope. This over-the-scope-clip system (OTSC), made of Nitinol, was tested in an experimental trial (domestic pig, 50-60 kg) for its applicability for perforation closure. In acute experiments, tight endoscopic closure of 10 perforations in five animals was demonstrated; perforations were made through repeat biopsy. In three further animals, the postoperative course was studied over a period of 2 weeks. Peritonitis was not found in any of these animals. The local healing result at the site of implantation was good. Clips were present 2 weeks after the procedure. In this experimental study, the OTSC clip system was found to be a simple and secure method of iatrogenic colon perforation closure.