Objective: To explore the clinical application value of enhanced recovery after surgery (ERAS) in the laparoscopic surgery for cholecystolithiasis comorbid with choledocholithiasis. Methods: The prospective study was conducted. The clinicopathological data of 52 patients with cholecystolithiasis comorbid with choledocholithiasis who were admitted to the Third Affiliated Hospital of Zunyi Medical University from September 2016 to September 2018 were collected. Patients were divided into 2 groups by random number table: patients in observation group received laparoscopic cholecystectomy + choledocholithotomy + choledochoscopic exploration + T-tube drainage (or primary suture of common bile duct) and perioperative management guided by the concept of enhanced recovery after surgery (ERAS), and patients in control group received traditional perioperative management. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) postoperative complications; (4) postoperative pain scores; (5) changes in hepatic function and blood routine during perioperative period. Follow-up using outpatient examination and telephone interview was performed to detect complications during the postoperative 6 months up to March 2019. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the paired t test or repeated ANOVA. Count data were described as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results: Fifty-two patients were screened for eligibility, including 20 males and 32 females, aged 25-68 years, with an average age of 53 years. There were 30 patients in the observation group and 22 in the control group. (1) Surgical situations: the operation time and volume of intraoperative blood loss were (133±19)minutes and (47±21)mL in the observation group, and (136±22)minutes and (49±23)mL in the control group, respectively, showing no significant difference between the two groups (t=-0.386, -0.211, P>0.05). (2) Postoperative situations: time to out-of-bed activity, time to initial food intake, time to first anal flatus, duration of postoperative hospital stay, and hospital expenses were (18±4)hours, (19±5)hours, (28±2)hours, (4.0±1.0)days, and (1.82±0.22)×10⁴ yuan in the observation group, and (29±7)hours, (46±9)hours, (37±4)hours, (6.6±1.6)days, and (2.25±0.29)×10⁴ yuan in the control group, respectively, showing significant differences between the two groups (t=-7.054, -14.169, -9.426, -6.582, -5.809, P<0.05). (3) Postoperative complications: 1 of 30 patients in the observation group had postoperative biliary leakage, with a postoperative complication rate of 3.3%, and was cured after symptomatic support treatment. Six of 22 patients in the control group had postoperative complication, with a postoperative complication rate of 27.3%, including 2 of biliary leakage, 1 of hemorrhage, 1 of abdominal infection, 1 of pulmonary infection, 1 of urinary infection, and they were cured after symptomatic support treatment. There was a significant difference between the two groups (χ²=4.358, P<0.05). (4) Postoperative pain scores: from postoperative 6 hours to 48 hours, the postoperative pain score changed from 2.4±0.7 to 1.9±0.9 in the observation group, and from 4.1±0.7 to 2.9±0.9 in the control group, respectively, showing a significant difference in the changing trend between the two groups (F=78.053, P<0.05). (5) Changes in hepatic function and blood routine during perioperative period: from preoperation to postoperative 3 days, levels of alamine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBil), and count of white blood cells in the observation group changed from (77±20)U/L to (53±12)U/L, from (85±22)U/L to (61±17)U/L, from (166±39)U/L to (55±24)U/L, from (40±13)μmol/L to (29±12)μmol/L, from (7.0±2.0)×10⁹/L to (6.8±1.9)×10⁹/L, and changed from (79±23)U/L to (62±14)U/L, from (88±24)U/L to (64±17)U/L, from (179±34)U/L to (74±29)U/L, from (45±13)μmol/L to (35±12)μmol/L, from (7.9±2.4)×10⁹/L to (7.5±1.9)×10⁹/L in the control group, respectively. The levels of ALT, AST, GGT, TBiL, and count of WBC showed increasing at postoperative 1 day, and decreasing at postoperative 3 days. There was no significant difference in the changing trend between the two groups (F=0.058, 0.471, 3.021, 1.593, 2.172, P>0.05). Conclusion ERAS is safe and effective in the laparoscopic surgery for choledocholithiasis comorbid with cholecystolithiasis.