Background and Aims Endoscopic ultrasound (EUS), magnetic resonance cholangiopancreatography (MRCP), and intraoperative cholangiogram (IOC) are the recommended diagnostic modalities for patients with intermediate probability for choledocholithiasis (IPC). The relative cost-effectiveness of these modalities in patients with cholelithiasis and IPC is understudied. Methods We developed a decision tree for diagnosing IPC (base case probability: 50%; range 10%-70%); patients with a positive test were modeled to undergo therapeutic ERCP. The strategies tested include (1) Laparoscopic cholecystectomy with IOC (LC-IOC), (2) MRCP, (3) single-session EUS + ERCP, and (4) separate session EUS + ERCP. Costs and probabilities were extracted from the published literature. Effectiveness was assessed by (1) assigning utility scores to health states, (2) the average proportion of true positive diagnosis of IPC, and (3) the mean length of stay (LOS) per strategy. Cost-effectiveness was assessed by extrapolating a net-monetary benefit (NMB), and average cost per true positive diagnosis. Results LC-IOC was the most cost-effective strategy to diagnose IPC (base-case probability of 50%) among patients with cholelithiasis in health state-based effectiveness analysis (NMB of $34,612), diagnostic test accuracy-based effectiveness analysis (average cost of $13,260 per true positive diagnosis), and LOS-based effectiveness analysis (mean LOS of 4.13) compared with strategy 2 (MRCP), 3 (single-session EUS+ERCP), and 4 (separate-session EUS+ERCP). These findings were robust on deterministic and probabilistic sensitivity analyses. Conclusion For patients with cholelithiasis with IPC, LC-IOC is a cost-effective approach that should limit preoperative testing and may shorten length of hospital stay. Our findings may be used to design institutional and organizational management protocols.