Pancreatic duct stent placement is increasingly performed for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP); however stents can result in injury especially in normal ducts. The clinical significance and outcomes of subsequent endoscopic therapy are unknown. This study was a retrospective review of the management of symptomatic stent-induced pancreatic duct injury following stent placement for prevention of post-ERCP pancreatitis in eight patients with previously normal pancreatic ducts. Subsequent treatment included pancreatic sphincterotomy, balloon dilation of stricture, and placement of multiple 35-Fr soft polymer pancreatic stents. All patients showed improvement or resolution of pancreatic strictures. Five patients had resolution or substantial improvement of pain, one patient showed a fair response with repeated ERCPs, and two patients failed to respond and underwent total pancreatectomy with islet autotransplantation. Pancreatic duct stent-induced ductal injury with significant clinical consequences can occur with conventional polyethylene stents. Endoscopic therapy is moderately effective but some patients develop irreversible damage. Caution should be used when placing standard polyethylene stents in normal ducts. Further research is required to identify safer materials and configurations of pancreatic stents.