Objective To investigate the clinical value of arterial first approach in laparoscopic pancreaticoduodenectomy (LPD). Methods The retrospective cohort study was conducted. The clinico-pathological data of 181 patients with pancreatic head and periampullay tumors who underwent LPD in the Affiliated Tongji Hospital of Huazhong University of Science and Technology between October 2014 and December 2016 were collected. Among 181 patients, 96 using arterial first approach and 85 using traditional approach were respectively allocated into the experimental group and the control group. Surgery was applied to patients in the same doctors′ team, and there were the same extent of surgical resection, range of lymph node dissection and digestive tract reconstruction. Observation indicators: (1) intraoperative situation; (2) postoperative situation; (3) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect the tumor-free survival up to February 2017. Measurement data with normal distribution were represented as ±s, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were described as M (range). Comparison of count data were analyzed using the chi-square test or Fisher exact probability. Results (1) Intraoperative situation: all the patients underwent successful LPD. Overall operation time and time of digestive tract reconstruction were respectively (268±20)minutes, (33±10)minutes in the experimental group and (285±25)minutes, (30±17)minutes in the control group, with no statistically significant difference between 2 groups (t=8.529, 2.741, P>0.05). Time of tumor resection with superior mesenteric venous invasion were respectively (216±13)minutes and (264±22)minutes in the experimental and control groups, with a statistically significant difference between the 2 groups (t=41.826, P 0.05). Volumes of intraoperative blood loss and blood transfusion were respectively (99±16)mL, (1.3±0.8)U in the experimental group and (131±27)mL, (2.8±1.2)U in the control group, with statistically significant differences between the 2 groups (t=3.670, 0.562, P 0.05). (2) Postoperative situation: time of drainage tube removal and duration of hospital stay were respectively (5.8±2.4)days, (18.3±6.3)days in the experimental group and (6.3±3.6)days, (19.6±7.1)days in the control group, with no statistically significant difference between the 2 groups (t=0.498, 1.305, P>0.05). Eleven patients in the experimental group had postoperative early complications, including 8 with grade A pancreatic fistula (4 combined with diarrhea, 2 combined with biliary fistula, 1 combined with delayed gastric emptying and 1 with single pancreatic fistula), 3 with grade B pancreatic fistula (2 combined with intra-abdominal hemorrhage and 1 combined with intra-abdominal infection). One patient with intra-abdominal hemorrhage in the experimental group died after treatment failure. Twelve patients in the control group had postoperative early complications, including 6 with grade A pancreatic fistula (2 combined with biliary fistula, 2 combined with delayed gastric emptying, 1 combined with diarrhea, 1 combined with digestive tract hemorrhage), 3 with grade B pancreatic fistula and intra-abdominal hemorrhage (2 combined with infection, including 1 death) and 3 with diarrhea. Other patients with complications were cured by symptomatic and supportive treatment. There was no statistically significant difference in overall complications between the 2 groups (χ2=0.287, P>0.05). Results of postoperative pathological examination showed that case with R0 resection was 93 and 76 in the experimental and control groups, with a statistically significant difference between the 2 groups (χ2=4.057, P 0.05). Conclusion Arterial first approach in LPD could significantly shorten the time of tumor resection of patients with superior mesenteric artery invading pancreatic head and periampullay region, significantly reduce the volumes of intraoperative blood loss and blood transfusion, and increase the rate of R0 resection. Key words: Pancreatic neoplasms; Periampullay neoplasms; Arterial first approach; Arterial first dissection; Pancreaticoduodenectomy; Laparoscopy