Background: The transvaginal natural orifice transluminal endoscopic surgery (vNOTES) applied in gynecology has been developed recent years and been evolving. In this study, we aimed to evaluate the feasibility and effect of the vNOTES hysterectomy for uterus ≥ 1 kilogram (kg).Methods: From January 2019 to March 2020, patients with benign indications in cases of uterus weighing ≥ 1kg, underwent vNOTES hysterectomy were studied retrospectively. The patients’ demographics, indications for surgery, operation outcomes and follow-up details were recorded. Results: 39 patients were performed vNOTES hysterectomy for large uterus (mean weight 1141.8 gram, range from 1000 to 1720), indications for surgery included bulky uterine myomas or adenomysosis. The mean age was 48 years (range 42-66) and mean BMI was 24 kg/m2 (range 18.4-38). Mean operating time was 123.3 minutes (rang 40-400) and the mean estimated blood loss was 206.7 milliliters (range 10-1300). The mean pain assessment was 2.1 (range 0-5). The mean length of stay was 2.4 nights (1-11). 1 patient experienced ureteral injury and was performed ureteral anastomosis. 3 patients were converted to vaginal-assisted trans-umbilicus single-port laparoscopy. The learning curve was analyzed to show that 20 cases were needed to achieve proficiency in vNOTES hysterectomy for large uterus ≥ 1 kg.Conclusion: Our preliminary experience suggested that vNOTES hysterectomy for large uterus weighing ≥ 1kg was feasible and safe, meanwhile this procedure had the advantages of all the minimal invasive approach such as fast recovery and aesthetic advantage.