Aims. We here investigated the association of different types of periampullary diverticula (PAD) with pancreaticobiliary disease and with technical success of endoscopic retrograde cholangiopancreatography (ERCP). Methods. A total of 850 consecutive patients who underwent their first ERCP were entered into a database. Of these patients, 161 patients (18.9%) had PAD and the age- and sex-matched control group comprised 483 patients. Results. PAD was correlated with common bile duct (CBD) stones (59.6% versus 35.0% in controls; P = 0.008) and negatively correlated with periampullary malignancy (6.8% versus 21.5% in controls; P = 0.004). The acute pancreatitis was more frequent (62.5%) in patients with PAD type 1 followed by PAD type 2 (28.9%, P = 0.017) and type 3 (28.0%, P = 0.006). No significant differences were observed in successful cannulation rate and post-ERCP complications among the 3 types of PAD. Type 1 PAD patients had less recurrence of CBD stones than did the patients who had type 2 or type 3 PAD (53.8% versus 85.7%; P = 0.043). Conclusions. PAD, especially type 1 PAD, is associated with an increased acute pancreatitis as well as occurrence and recurrence of CBD stones. PAD during an ERCP should not be considered as an obstacle to a successful cannulation.