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Abstract Background: Common bile duct (CBD) stones, also referred to as choledocholithiasis, represent a significant clinical burden within the spectrum of gallstone disease, affecting between 10% and 20% of patients with symptomatic cholelithiasis. While the vast majority of these stones are amenable to standard endoscopic retrograde cholangiopancreatography (ERCP), approximately 10% to 15% of cases involve "difficult" stones that present unique technical challenges due to their size, location, or associated anatomical variations. Objective: This research report aims to evaluate the integrated management strategies for difficult CBD stones, comparing the technical efficacy, clinical success rates, and complication profiles of advanced endoscopic techniques, percutaneous transhepatic biliary drainage (PTBD), and surgical interventions. The study specifically investigates the epidemiological variations in India and Central Asia to provide context for localized management protocols. Methods: A systematic review and comparative analysis of existing clinical registries, randomized controlled trials, and international society guidelines (ESGE, ASGE, BSG) were conducted. Data sources included 84 unique research snippets and academic documents spanning the period from 2000 to 2024. The analysis focused on stone clearance rates, procedural safety, and economic outcomes across diverse healthcare settings. Results: Findings indicate that advanced endoscopic techniques such as endoscopic papillary large balloon dilation (EPLBD) and cholangioscopy-guided lithotripsy achieve clearance rates exceeding 90%. However, laparoscopic common bile duct exploration (LCBDE) demonstrates superior efficacy for large, multiple, or impacted stones (88.89% clearance) while offering a significant cost advantage of approximately $2,046 per patient compared to a two-stage approach. Epidemiological data highlight a high prevalence of cholesterol stones in North India and pigment stones in South India and Central Asian ethnic groups. Conclusion: Management of difficult CBD stones requires a tailored, algorithmic approach. While advanced ERCP remains the primary minimally invasive intervention, single-stage LCBDE is highly effective for complex cases and resource-limited settings. A multidisciplinary strategy integrating endoscopy and surgery is essential for optimizing patient outcomes. Keywords: Choledocholithiasis, ERCP, LCBDE, EPLBD, Biliary Lithotripsy, Hepatobiliary Epidemiology.