Objective: To investigate the clinical application of combined multiple artery-first approach to pancreatoduodenectomy. Methods: The clinical data of 53 patients who were diagnosed with peripancreatic head tumor at Department of Biliary-Pancreatic Surgery of Second Affiliated Hospital of Harbin Medical University between June 2013 and June 2015 was retrospectively analyzed.Pancreatic enhanced CT scan, magnetic resonance cholangiopancreatography, ultrasonography and tumor marker detection were applied for all the patients preoperatively.The 53 patients were operated by combined multiple artery-first approach(superior+ posterior approach, superior+ inferior approach, posterior+ inferior approach, superior+ posterior+ inferior approach) according to individualized therapeutic concept.And 42 patients underwent pancreatoduodenectomy, 9 patients underwent palliative operation and 2 patients just received exploratory operation. Results: Forty-two peripancreatic head tumor patients underwent pancreatoduodenectomy by applying combined multiple artery-first approach.The median operation time and intraoperative blood loss were (5.4±3.1)hours and (366±297)ml and the harvested lymph node and duration of hospital stay were 19±5 and (14.0±5.6)days.Nine patients underwent "total mesopancreas excision" and the rate of postoperative pancreatic fistula and R0 resection were 38.1% and 88.1%. Anomalous origin hepatic right artery was detected in one patients during the operation and no death occurred within 30 days postoperatively. Conclusion: According to the tumor location and patient's condition, individualistically applying combined multiple artery-first approach can reduce intraoperative blood loss, terminate unnecessary surgery, detect anomalous origin artery, make the tumor resection more radical and pancreatoduodenectomy more safety.