Transvaginal natural orifice translumenal endoscopic surgery (NOTES) is a new diagnostic and potentially therapeutic method of surgical endoscopy. The first case of NOTES transvaginal cholecystectomy in a morbid obese patient in the literature is described. IRB approval was obtained at the institution for transvaginal NOTES clinical trials. A 58-year-old female patient with cholelithiasis, hypertension, and type II diabetes, and BMI of 35.8 kg/m(2) was submitted to the technique. After transvaginal access, a two-channel gastroscope was introduced into the abdominal cavity along with a laparoscopic trocar. There were 2 umbilical punctures for use of 3 mm laparoscopic equipment. Operative time was 85 min. There was no use of postoperative analgesia, and the patient was discharged on the third postoperative day. Transvaginal NOTES is a feasible alternative method for cholecystectomy in the morbidly obese, although available technology is limited for natural orifice surgery.