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BACKGROUND AND STUDY AIMS: Cholecystectomy using a rigid-hybrid transvaginal natural orifice transluminal endoscopic surgery (NOTES) approach (tvNCC) reduces abdominal wall incisions and might decrease surgical trauma by combining endoluminal access and laparoscopic techniques. We assessed the feasibility and safety of rigid-hybrid tvNCC in routine practice for symptomatic cholecystolithiasis or acute cholecystitis in a patient population with low selection. PATIENTS AND METHODS: From September 2008 to July 2009, all female patients with cholecystectomy indications were evaluated for tvNCC. Exclusion criteria were: refusal of tvNCC; inability to give informed consent; gynecological or urological contraindications; lack of preoperative gynecological examinations; need for cholangiography/choledochus revision; anesthesiological contraindications to pneumoperitoneum; liver failure; or coagulopathy. Age, obesity, previous surgery, or degree of gallbladder inflammation were not exclusion criteria. Preoperative and 2-weeks' postoperative gynecological examinations were performed. Sexual function was assessed preoperatively and at 6 weeks postoperatively. RESULTS: 102 of 137 consecutive patients (74.5 %) with symptomatic cholecystolithiasis (n = 74) or cholecystitis (n = 28) were scheduled for rigid-hybrid tvNCC with nine different surgeons. Patient mean age was 52.3 +/- 17.8 years (range 18 - 87) and mean body mass index 27.3 +/- 6.3 kg/m (2) (17.6 - 43.8). Two patients had conversion to conventional laparoscopic cholecystectomy. There were no intraoperative complications. Two major complications occurred: one stroke and one herniation within the transumbilical access. Minor complications were reported in 13 patients (12.7 %) and there were no serious postoperative gynecological findings. At 6 weeks postoperatively, there were fewer dyspareunia symptoms than preoperatively ( P = 0.049). CONCLUSIONS: Rigid-hybrid tvNCC is feasible and safe in routine practice for symptomatic cholecystolithiasis and acute cholecystitis.