Objective The objective of this study is to evaluate the effect of enhanced recovery after surgery (ERAS) in the perioperative period of pancreatoduodenectomy. Methods This article conducted the forward-looking analysis on the information of 227 patients undergoing the pancreatoduodenectomy in West China Hospital from January 2016 to June 2017, and then compared the differences between the patients subjected to ERAS (ERAS group) and thosesubjected to regular measures (control group) with respect to time of setting in sickbed, time of mobilizing out ofsickbed, time of starting drink water, time of resumption of diet, exhaust time, defecation time, the time of nasogastric tube, postoperative hospitalization duration and expenses, postoperative complications, and postoperative pain scores. Results ① Postoperative indexes: by comparison of the ERAS group and the control group, it was found that the ERAS group had shorter (or lower) time of setting in sickbed, time of mobilizing out of sickbed, time of starting drink water, time of resumption of diet, exhaust time, defecation time, the time of nasogastric tube, postoperative hospitalization duration and expenses (P<0.05). ② Postoperative complications: of all postoperative complications, including pancreatic fistula, postoperative hemorrhage, delayed gastric emptying, biliary fistula, abdominal infection, incision complication, lung infection, and heart complication were without statistically significant differences (P>0.05) between the 2 groups.③ Reoperation and readmission: there was no significant difference on the incidences of reoperation and readmission between the 2 groups (P>0.05). ④ Postoperative pain scores: except 22 : 00 of the 6-day after operation, the pain scores in the ERAS group were all lower than those in the control group at 2 h and 8 h after operation, and the time points of 1–6 days after operation (8 : 00, 16 : 00, and 22 : 00), with statistically differences (P<0.05). Conclusion Without increasing the incidence of complications, ERAS may speed up the rehabilitation of patients undergoing the pancreatoduodenectomy and mitigate the pain of patients.