BackgroundThe purpose of the current study is to compare the quality of surgical condition of combined epidural-general anesthesia (EGA) versus general anesthesia (GA) in patients undergoing transvaginal natural orifice transluminal endoscopic surgery (vNOTES). MethodsPatients undergoing vNOTES were randomly allocated to receive GA or EGA. The primary outcome was evaluate the quality of surgical condition. We further assessed patients’ medical data regarding the need and consumption of intraoperative analgesics and vasoactive drugs. The visual analogue scale (VAS) and postoperative nausea and vomiting (PONV) scores were assessed at 2 h and 24 h postoperatively. We have registered the number of patients who needed rescue analgesics and antiemetics within 24 h after surgery. ResultsThe scores of the quality of surgical condition was 1.9 ± 0.8 in the GA group and 1.4 ± 0.7 (P = 0.001) in the EGA group. The PONV scores were not significantly different in the first two 2 h following surgery between the groups. The obviously differences in the PONV scores between the EGA group and GA group were detected at the 24th postoperatively. Moreover, there were no significant differences in the consumption of atropine, sufentanil, cisatracurium, propofol, sevoflurane and neostigmine between the two groups. Regarding the duration of extubated time, operative time, duration of anesthesia time and postoperative length of hospital stay (PLOS), our findings did not showcase significant differences between the two groups. Similarly, we did not detect significant changes in the postoperative pain at the two time points between the groups. ConclusionOur results showed that compared with GA, EGA improved the quality of surgical condition in patients undergoing vNOTES. As epidural block is an additional invasive procedure with its attendant risks, we should weigh the pros and cons when combined epidural-general anesthesia is used for vNOTES in the future. Trial registrationThis study was registered at Chinese Clinical Trial Registry chictr.org.cn (http://www.chictr.org.cn/) with No. 2000032406 on April 27, 2020.