Objective: To retrospectively analyze the anesthesia effect and safety of combined spinal-epidural anesthesia (CSEA) in single-port laparoscopic gynecological surgery. Methods: From December 2019 to August 2021, 60 patients who underwent gynecological single-port surgery in our hospital were selected as the research objects. According to the different methods of anesthesia, they were divided into an observation group of 30 cases (using CSEA) and a control group of 30 cases (using epidural anesthesia). Results: The excellent and good rate of anesthesia in the observation group was 90.00%, which was significantly higher than 73.33% in the control group (P=0.023). the difference was statistically significant (P=0.023). There was no significant difference in blood pressure or heart rate between the two groups when they entered the operating room (T0), when anesthesia started (T1), and 10 min after anesthesia started (T2) (P>0.05). However, the changes in blood pressure and heart rate in the observation group were more stable than those in the control group at 20 min (T3) and 30 min (T4) of the onset of anesthesia. There was no significant difference in the total incidence of adverse events between the observation group and the control group (P>0.05). Conclusion: Compared with epidural anesthesia, CSEA has higher safety, faster onset time, fewer complication and higher clinical application value in single-port laparoscopic gynecological surgery.