The purpose of this study was to evaluate the feasibility of hybrid natural orifice translumenal endoscopic surgery (NOTES) transvaginal cholecystectomy in a porcine model of acute cholecystitis. We have developed an experimental model of acute cholecystitis in 8 female pigs (33.37±3.11 kg) through the surgical occlusion of the common bile duct. After 4 days, hybrid NOTES cholecystectomy was performed in all animals with the assistance of only one 5 mm trocar. The transvaginal approach and the abdomen exploration were performed without any complication. The hybrid NOTES cholecystectomy was successfully completed in all animals. The mean operative time was 76.50±10 minutes. Gallbladder rupture appeared in 2 cases, and there was no bleeding or laceration of adjacent organs. Our experiments showed the feasibility of hybrid NOTES cholecystectomy in an experimental model of acute cholecystitis. Additional research and training on experimental models of pathology will be necessary to validate NOTES surgery.