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Background: Treatment of common bile duct stones (CBDS) includes laparoscopic cholecystectomy (LC) with either laparoscopic common bile duct exploration (LCBDE) or perioperative endoscopic retrograde cholangiopancreatography (ERCP). The main objective of this study was to identify predictive factors for the failure of upfront and exclusive surgical treatment by LCBDE., Methods: This is a single-center, retrospective study on patients with CBDS and operated for LC between 2007 and 2019. The use of intra- or postoperative endoscopy for CBD clearance within 6 months after surgery was considered as failure of LCBDE. Predictors for the failure of LCBDE were investigated and outcomes were compared., Results: Among 222 operated patients, LCBDE was successfully performed in 173 patients (78%) and 49 (22%) required ERCP with sphincterotomy (intraoperative (n=29) or postoperative (n=20)). Independent risk factors for surgical failure were male sex (OR: 2.525 (1.111-5.738); p=0.027), anesthesia induction time ≥ 4 p.m. (OR: 4.858 (1.731-13.631); p=0.003), pediculitis (OR: 4.147 (1.177-14.606); p=0.027), and thin CDB < 4mm (OR: 11.951 (3.562-40.097), p< 0.0001). Age, ASA score, cystic anatomy, presence of cholecystitis, and the surgeon's experience were not identified as predictors for surgical failure. A general anesthesia number >1 (6% vs. 33%; p < 0.0001), length of initial stay (6 [1-42] vs. 8 [2-27], p=0.012), total length of hospitalization (6 [1-45] vs. 9 [2-27]; p=0.010), and the rate of emergency readmissions (3.5% vs. 12.2%; p=0.027) were significantly higher in the LCBDE failure group., Conclusions: Upfront LCBDE for CBDS was associated with improved outcomes compared to intra-/postoperative ERCP recourse. Male sex, pediculitis, thin CBD, and surgery later than 4 p.m were associated with LCBDE failure and the need for endoscopic treatment., Registration Number and Agency: The present retrospective study was approved by our local ethics committee and was declared on ClinicalTrials.gov (ID: NCT04467710)., (© 2023. The Society for Surgery of the Alimentary Tract.)