Objective: To determine the clinical application value of laparoscopic pancreaticoduodenectomy (PD) with an uncinate process approach. Methods: The clinical data of 12 patients undergoing laparoscopic PD with uncinate process approach since February 2010 were reviewed. The essential feature of the operation was dissection of the uncinate process and the mesentery upwards along the right side of the superior mesenteric artery from the horizontal part of the duodenum, and then proceeding to conduct the other surgical procedures in the conventional order. Results: Of the 12 patients, 2 cases were converted to open surgery, and remaining 10 cases had successful laparoscopic PD. The operative time for laparoscopic PD was 240 to 340 min with an average of 280 min, the intraoperative blood loss was 150 to 1 200 mL with an average of 300 mL, and the number of dissected lymph nodes was 9 to 15 with an average number of 10. Postoperative pathological examination showed negative surgical margins. Postoperative pancreatic leakage and bile leakage occurred in 2 patients and 1 patient respectively, which were all cured after treatment. Conclusion: Laparoscopic PD with uncinate process-first approach is a safe, feasible and effective surgical procedure.