Objective To investigate the effect of single-person and two-person guidewire papillary intubation in endoscopic retrograde cholangiopancreatography (ERCP).Methods General data of 445 patients who underwent ERCP treatment for pancreatic biliary diseases from February 2019 to February 2021 were collected to compare the success rate of ERCP intubation and postoperative complications between the two methods, then analyze the influencing factors of hyperamylasemia.Results The overall success rate of intubation was 97.3%, of which the rate of single intubation was 97.5% and that of double intubation was 97.1%, there was no significant difference between the two groups (P = 0.782). Pancreatitis occurred in 22 cases (4.9%) and hyperamylasemia in 105 cases (23.6%), there was no significant difference in the incidence of postoperative complications between the two methods of intubation (P > 0.05). However, the time of intubation [(7.15 ± 0.48) min vs (10.70 ± 0.71) min], ERCP completion time [(19.24 ± 1.26) min vs (23.11 ± 1.64) min] and hospital stay (9.0 d vs 11.0 d) in the single-person intubation group were significantly faster than those in the two-person operation group, there were statistically significant difference (P < 0.05).Conclusion There is no significant difference in the success rate of ERCP intubation and the incidence of postoperative complications between the two methods of nipple intubation. Single-person intubation technique is beneficial to shorten the intubation time, reduce the number of guidewire entering the pancreatic duct, reduce nipple injury, reduce the incidence of postoperative complications, and thus reduce the length of hospital stay because it does not require close cooperation of the assistant.