The prevalence of periampullary diverticulum (PAD) is relatively high in patients who undergo endoscopic retrograde cholangiopancreatography (ERCP). It is currently unclear if the presence of PAD impacts the success, difficulty, and complication rates of ERCP. The aim of the study is to investigate and compare the success rate, procedure difficulty, and complication rate between patients with or without PAD. Patients with PAD were further analyzed according to location and size. A total of 548 ERCP procedures were performed at our endoscopy center from 2015 to 2016. Those patients with previous ERCP, inability to locate the ampulla or abandoned procedure were excluded. 357 procedures were analyzed. A t test (normally distributed) or Mann‐Whitney U test (skewed) for continuous data and chi‐square or fisher's exact test for categorical data. A total of 116 were found to have PAD. The ampulla was located within the diverticulum in 8.9%, on the edge in 38.9%, and near in 52.2%. 64.3% of the PAD was large and 35.7% small. Patients with PAD were significantly older (P < .001) and more likely to undergo ERCP for common bile duct stone (P = .007). There was no difference in ERCP grade, cannulation difficulty, cannulation success, procedure time, and complication rate between the two groups. Location and size of PAD also did not impact ERCP. The presence of PAD did not affect ERCP cannulation rates, increase the difficulty of cannulation or caused more complications.