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Background and Aims Management of symptomatic pancreatic ductal (PD) stones in chronic calcific pancreatitis (CP) remains challenging. Stones >5 mm typically require fragmentation prior to extraction. Extracorporeal shockwave lithotripsy (ESWL) combined with endoscopic retrograde cholangiopancreatography (ERCP) is well-established, while ERCP-assisted pancreatoscopy–guided intraductal lithotripsy has emerged as an alternative minimally invasive approach. We compared the cost-effectiveness of ESWL + ERCP, ERCP + pancreatoscopy, and surgical management for large PD stones using a decision-analytic framework.Methods A patient-level, discrete-time Markov model was developed following a targeted literature review. Three treatment strategies were assessed:ESWL followed by ERCP,ERCP with pancreatoscopy-guided lithotripsy, andSurgical management, including lateral pancreatojejunostomy, duodenal-preserving pancreatic head resections (Beger, Frey), and pancreaticoduodenectomy.Transition probabilities and HRQoL estimates were sourced from published data. Outcomes included costs, quality-adjusted life years (QALYs), and net monetary benefit (NMB). Deterministic and probabilistic Monte Carlo simulations (1,000 iterations each) were performed. One-way and probabilistic sensitivity analyses assessed parameter uncertainty.Results In the base-case analysis, ESWL + ERCP (Cost: £3,859 [$5,100], 0.98 QALYs) dominated ERCP + pancreatoscopy(£4,856 [$6,420], 0.54 QALYs) and surgery (£6,910 [$9,130], 0.45 QALYs). At a UK willingness-to-pay threshold of £30,000/QALY, ESWL + ERCP generated the highest NMB (£25,597 [$33,960]). Deterministic analysis yielded similar Results ESWL + ERCP (Cost £3,943 [$5,210], 0.99 QALYs) dominated alternatives.Probabilistic sensitivity analysis confirmed ESWL + ERCP as the most cost-effective strategy (mean Cost £3,845 [$5,080], 97% CI £3,190–£4,473; Effectiveness 0.98 QALYs, 97% CI 0.89–1.06). ERCP + pancreatoscopy and surgery were less effective and more costly. Threshold analysis showed pancreatoscopy would require >93% ductal clearance efficacy to match ESWL + ERCP. Incorporating pancreatoscopy into the ESWL + ERCP pathway reduced costs by 3% and increased QALYs by 1%. Without ESWL, ERCP + pancreatoscopy remained more cost-effective than surgery.Conclusions Minimally invasive endoscopic strategies—particularly ESWL combined with ERCP—are substantially more cost-effective than surgical management for large pancreatic duct stones. Pancreatoscopy may offer incremental benefit in selected cases but requires markedly higher clearance rates to rival the cost-effectiveness of ESWL + ERCP.