BackgroundThe safety and efficacy of intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct plus laparoscopic cholecystectomy (ENBD+ LC+ LCBD) for cholecystolithiasis combined with common bile duct stones (CBD stones) are uncertain. MethodsThe meta-analysis search was performed using PUBMED, OVID, EMBASE, and Cochrane database. All studies comparing ENBD+ LC+ LCBD and ECRP/EST+ LC from 1990 to 2018 were included. Pooled effect was calculated using the fixed and random effects models when necessary. ResultsA total of 5 trails included 700 patients with two different treatments (ENBD+ LC+ LCBD and ECRP/EST+ LC) were identified. The ENBD+ LC+ LCBD group had less total complications or adverse events (RR = 0.268, 95% CI:0.138–0.520, I2=0.0%, P < 0.001). And subgroup analysis of total complications exposed that although ENBD+ LC+ LCBD group developed more of biliary leak, there was no significance (RR = 3.890, 95% CI:0.88–17.25, I2=0.0%, P = 0.074). Meanwhile, there were lower rates of retained stones (RR = 0.272, 95% CI:0.09–0.85, I2=0.0%, P = 0.026), postoperative bleeding (RR = 0.129, 95% CI:0.02–0.75, I2=0.0%, P = 0.022) and pancreatitis (RR = 0.127, 95% CI:(0.04–0.43, I2=0.0%, P = 0.001) in ENBD+ LC+ LCBD group. Although operative time (WMD=32.465, 95% CI:0.468–64.61, I2=98.6%, P = 0.047) showed significant difference, sensitivity analysis didn’t confirm the robustness of the results. Futhermore, it seemed that ENBD+ LC+ LCBD group had a shorter length of postoperative hospital stay (WMD=-1.880, 95% CI:-3.063–-0.696, I2=94.4%, P = 0.002) and less expenditure of hospitalization (WMD=-430.439, 95% CI:-704.620–-156.258, I2=92.3%, P = 0.002). ConclusionsIt is safe and efficient by intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct for patients with cholecystolithiasis combined with CBD stones. Legal entity responsible for the studyXiujun Cai. FundingOpening Fund of Engineering Research Center of Cognitive Healthcare of Zhejiang Province (No.2018KFJJ09). DisclosureAll authors have declared no conflicts of interest.