AIM: To investigate the effectiveness and safety of limited endoscopic sphincterotomy (EST) plus large balloon dilation (LBD) for removing choledocholithiasis in patients with periampullary diverticula (PAD).METHODS: A total of 139 patients with common bile duct (CBD) stones were treated with LBD (10-20 mm balloon diameter) after limited EST. Of this total, 73 patients had PAD and 66 patients did not have PAD (controls). The results of stone removal and complications were retrospectively evaluated.RESULTS: There were no significant differences between the PAD and the control groups in overall successful stone removal (94.5% vs 93.9%), stone removal in first session (69.9% vs 81.8%), mechanical lithotripsy (12.3% vs 13.6%), and complications (11.0% vs 7.6%). Clinical outcomes were also similar between the types of PAD, but the rate of stone removal in first session and the number of sessions were significantly lower and more frequent, respectively, in type B PAD (papilla located near the diverticulum) than controls [23/38 (60.5%) vs 54/66 (81.8%), P = 0.021; and 1 (1-2) vs 1 (1-3), P = 0.037, respectively] and the frequency of pancreatitis was significantly higher in type A PAD (papilla located inside or in the margin of the diverticulum) than in controls (16.1% vs 3.0%, P = 0.047).CONCLUSION: Limited EST plus LBD was an effective and safe procedure for removing choledocholithiasis in patients with PAD. However, some types of PAD should be managed with caution.