Objective To investigate the application effect of LEER (less pain, early move, early eat, and reassuring) mode in laparoscopic pancreaticoduodenectomy (LPD). Methods The clinical data of patients who underwent LPD in our hospital from March 2020 to March 2022 were retrospectively analyzed. Forty patients treated with the traditional mode during the perioperative period were classified as the traditional group, and 47 patients treated with the LEER mode were classified as the LEER group. The perioperative indicators, inflammatory stress indicators, immune indicators, nutritional indicators and postoperative complications were compared between the two groups. Results The visual analogue scale (VAS) score and hospitalization cost of the LEER group were lower than those of the traditional group (P<0.05). The postoperative ambulation time, anal exhaust/defecation time, drainage tube removal time, time to normal diet and hospital stay in the LEER group were shorter than those of the traditional group (P<0.05). Compared with preoperative, the WBC count and C-reactive protein (CRP) level of patients in the two groups increased after operation, but the changes of WBC count and CRP level in the LEER group were smaller than those in the traditional group (P<0.05). The IgA, IgM and IgG levels of patients in the two groups were not statistically different before and after operation (P>0.05), and the postoperative IgA, IgM and IgG of patients in the LEER group were higher than those in the traditional group (P<0.05). The change values of IgM and IgG in the LEER group were smaller than those of the traditional group (P<0.05), but there was no statistical difference in the change value of IgA between the two groups before and after operation (P>0.05). Compared with preoperative value, postoperative prealbumin (PA) and lymphocyte (LYM) levels in the two groups were decreased (P<0.05). The postoperative PA and LYM levels in the LEER group were higher than those in the traditional group (P<0.05). but the change value of PA before and after operation in the LEER group was smaller than that in the traditional group (P<0.05). There was no statistical difference in the change of LYM between the two groups before and after operation (P>0.05). The incidence of postoperative complications in the LEER group was 8.5% (4/47), and that in the traditional group was 35.0% (14/40). The incidence of postoperative complication in the LEER group was significantly lower than that in the traditional group (P=0.002). Conclusion Applying LEER mode in LPD can promote postoperative recovery of the patients, reduce postoperative stress response, improve nutritional status and protect immunity in the patients.