Objective: To investigate the clinical value of using enhanced recovery after surgery (ERAS) protocols in perioperative period of pancreaticoduodenectomy (PD). Methods: The clinical data of 42 patients undergoing radical PD in the Affiliated Tumor Hospital of Zhengzhou University from June 2015 to December 2016 were retrospectively analyzed. All patients received ERAS management during perioperative period. The clinical variables that included postoperative complications, length of hospitalization and readmission were recorded. Results: On postoperative day (POD) 1, all patients underwent routine removal of urinary catheter, of whom, 2 cases had catheter indwelling due to prostatic hyperplasia, 22 patients (52.4%) successfully ambulated and 10 patients (23.8%) achieved the scheduled activity standard. On POD 2, routine gastric tube removal was performed, but the gastric tube was reintroduced in 5 cases for occurrence of delayed gastric emptying and 30 cases (71.4%) tolerated the liquid diet. On POD 3, abdominal drainage tube was removed in 35 cases (83.3%). On POD 4, 33 patients (78.6%) tolerated solid diet intake. The postoperative complications included pancreatic leakage in 3 cases, bile leakage in 1 case, bleeding in 1 case, abdominal fluid collections in 3 cases, delayed gastric emptying in 4 cases, and lung infection in 1 case, with an overall incidence of postoperative complications of 31.0%, which were all resolved after symptomatic treatment. No death occurred. The median length of hospitalization was 10 (8–35) d. Three patients (7.1%) patients required hospital readmission within 30 d of discharge, and of whom, one was for gastric insufficiency, one for abdominal fluid collection with infection and one for biliary tract infection. Conclusion: Application of ERAS in perioperative period of PD is safe and feasible, which can reduce the length of hospitalization without increase of incidence of postoperative complications and readmission rate.