The central dogma of pain in patients with chronic pancreatitis revolves around the pathophysiology of ductal hypertension owing to stones that obstruct the pancreatic duct. Conventional modalities available to decompress the pancreatic duct are occasionally limited by failed selective pancreatic duct cannulation during endoscopic retrograde cholangiopancreatography. We describe a novel endoscopic approach of EUS-guided laser lithotripsy to assist in pancreatic duct (PD) stone fragmentation in two symptomatic patients with underlying chronic pancreatitis who had failed PD cannulation and extracorporeal shock wave lithotripsy (ESWL). In both cases, a 365-micrometer LightTrail TracTip Holmium laser fiber was advanced within a 19G endoscopic ultrasound aspiration needle (Expect Slimline (SL), Boston Scientific, Marlborough, Massachusetts, United States) under endoscopic ultrasound (EUS) guidance to fragment the PD stones. There were no procedure-related complications encountered and follow-up after 1 month of the procedure revealed significant reduction in abdominal pain scores. To the best of our knowledge, these are the first reported cases of EUS-guided laser lithotripsy performed for PD stones. Our approach of performing laser lithotripsy under EUS guidance obviates the need for an ESWL procedure; however, it is technically more challenging and requires precision to avoid injury to the pancreas. Further prospective studies are required to evaluate the safety and efficacy of this novel approach and its applicability as either a rescue procedure or in tandem with conventional pancreatic endotherapy modalities.