Objective To compare the efficacy and safety of combined epidural/general anesthesia (CEGA) versus total intravenous anesthesia (TIVA) for laparoscopic cholecystectomy. Methods Forty patients were assigned to group TIVA and group CEGA by random digits table with 20 cases in each. The systolic and diastolic arterial pressure,heart rate, oxygen saturation,Steward score, visual analogue scale (VAS) score and adverse reaction were monitored. Results Steward score 4,6 min after operation in group CEGA [(4.5 ±0.6), (5.7 ±0.2) scores] was higher than that in group TIVA [(2.8 ±0.4), (4.1 ±0.5)scores](P ＜ 0.05 ). The VAS score 2,3,4 h after operation in group CEGA [( 1.8 ± 0.3 ), (1.5 ± 0.4), (1.7±0.3 ) scores] was lower than that in group TIVA [( 3.2 ± 0.5 ), ( 3.7 ± 0.4), (4.2 ± 0.6) scores] (P＜0.05 ).There was no significant difference in abdomen pain, shoulder pain and adverse reaction between two groups.The incidence of postoperative side effects was lower in both groups (P ＞ 0.05). Conclusions The use of CEGA for laparoscopic cholecystectomy seems to be effective and safe, and to offer some advantages as compared to TIVA alone. CEGA can control pain due to CO2-induced peritoneal irritation, provide excellent infra-operative and postoperative analgesia. CEGA does not require the use of intraoperative intravenous opioids and shortens recovery time, without increasing the incidence of adverse reaction.