Objective: To explore the feasibility and surgical outcomes of robot-assisted vaginal natural orifice transluminal endoscopic surgery (RA-vNOTES) for women suffering from gynecologic disease. Design: Large retrospective case series. Setting: Single academic tertiary care hospital in Houston, Texas, USA. Population: 298 adult women with gynecologic disease who underwent RA-vNOTES. Methods: We performed an observational study reporting and analyzing perioperative outcomes of 298 patients with gynecologic disease who underwent RA-vNOTES in a single institution from June 2019 and August 2024. Main Outcome Measures: Surgical outcomes and complications. Results: 298 patients with a median age of 41 years and median BMI of 29 kg/m 2, underwent RA-vNOTES. The primary indications for surgery were endometriosis (43.62%), chronic pelvic pain (11.07%), abnormal uterine bleeding (20.81%), and uterine fibroid (14.77%). 286 of 298 (95.97%) patients had a hysterectomy. The median total operative time was 138 minutes, with port placement time of 5 minutes, dock time of 3 minutes and robot console time of 63 minutes. Median estimated blood loss was 50 mL. Endometriosis resection of all stages was performed in 192 of 298 (64.43%) patients. Three cases (1.01%) were converted to laparoscopic surgery. One case was converted to robot-assisted single incision plus one port laparoscopic surgery (SILS plus one) and two cases were converted to robot-assisted multi-port surgery. The total complication rate was 17.45% (52 cases), of which 2.1% (6 cases) were intraoperative complications and 15.44% (46 cases) were postoperative complications. Conclusion: Our findings indicate that RA-vNOTES is a feasible and less invasive option for gynecologic diseases.