Objective. To assess outcome and safety of 571 hybrid natural orifice transluminal endoscopic surgery (NOTES) cholecystectomies. Methods. We retrospectively analyzed all consecutive NOTES cholecystectomies performed at our center between June 2009 and January 2018. All procedures were performed using a hybrid transvaginal technique, including an umbilical small-size trocar. End points, calculated at discharge, 30 and up to 90 days postoperatively, included intra- and postoperative morbidity assessed by the validated Clavien–Dindo classification and the Comprehensive Complication Index (CCI). Special focus was held on outcome and necessity of pre- and postoperative gynecological examinations. Results. We performed 571 hybrid NOTES cholecystectomies within 9 years. The vast majority were elective, 9.6% were emergency cholecystectomies. 6.7% of patients developed at least one complication until discharge, most of them minor (≤grade II). 30- and 90-day complication rates were 10.7% and 11%, respectively. Mean CCI at discharge and postoperative days 30 and 90 was 1.45 (±6.4), 2.3 (±7.7), and 2.4 (±7.8), respectively. Major complications (≥grade IIIa) occurred in 1.6% of patients, and 4 patients required emergency reoperation. No mortality was observed. In 9.8%, an additional abdominal trocar was placed. All patients underwent routine gynecological examination, whereof only 5 were rejected for transvaginal access preoperatively. In no case transvaginal access was discontinued intraoperatively due to gynecological disease. Conclusion. Hybrid NOTES transvaginal cholecystectomy represents a safe and feasible alternative to standard laparoscopic cholecystectomy. Preoperative gynecological examination is no longer routinely necessary, as intraoperative assessment is adequate.