Background: Accidental splenic laceration and hemorrhage during transgastric access to the peritoneal cavity or organ resection during NOTES can lead to life-threatening consequences. The natural orifice approach may need to be aborted in these circumstances for a standard laparoscopy or laparotomy. Aim: To determine the feasibility of endoscopically managing intra-operative splenic laceration and hemorrhage from accidental trauma during NOTES. Methods: 60 - 80 lbs pigs were used for the study and underwent transcolonic endoscopic surgery under general anesthesia. The spleen was located by direct visualization and intentional lacerations were made using endoscissors and a needle-knife. Cuts of varying length (0.5 cm, 1 cm, 2 cm, and 2 cm × 2 cm cruciate laceration) were made. All lacerations produced active and persistent bleeding. The site was lavaged with sterile water and persistent spurting or oozing of blood was confirmed. A standard endoscopic 7 Fr bipolar electro-hemostasis catheter (Gold Probe, Boston Scientific) at 30 - 40 W was used to achieve hemostasis. The colonic incision was then closed using endoscopic clips (Resolution Clip, Boston Scientific). Necropsy was performed immediately after surgery in acute cases and at the end of the one week survival period per protocol. Site of laceration and the peritoneal cavity was examined for bleeding, abscess and damage to surrounding structures. Results: Nine intentional splenic lacerations were performed in 6 live anesthetized animals (4 acute and 2 survival studies) to mimic accidental splenic injury. Bleeding was successfully managed endoscopically using standard bipolar cautery in all animals. Persistent pressure was applied with the bipolar probe for coaptive coagulation, and intermittent lavage was performed to visualize the site of bleeding. Maximum time required for hemostasis was 25 minutes. Survival animals had an uncomplicated post-operative course and were euthanized per protocol. There was no evidence of intraperitoneal bleeding or abscess at necropsy. The omentum was seen adherent to the spleen in one survival animal at the site of laceration. Conclusion: We demonstrate the successful management of intra-operative splenic laceration and hemorrhage during NOTES using standard endoscopic techniques, avoiding the need for laparoscopic exploration or laparotomy.