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Laparoscopic pancreaticoduodenectomy (LPD), a surgical option for nonpancreatic periampullary adenocarcinoma (NPPA), is a complex procedure that has become increasing popular. However, there is no consensus as to whether this technique should be performed routinely. Our aim was to evaluate the outcomes of LPD compared with open pancreaticoduodenectomy (OPD).From October 2010 to September 2015, 58 LPDs were performed to treat NPPA and were compared with 58 OPDs, which can theoretically be carried out by laparoscopic approach. Patients were also matched based on their demographic data and pathologic diagnosis. Demographic information, intraoperative and postoperative data, pathologic data, and follow-up evaluation data were collected at our center.All patients had a median follow-up of 34 months (range, 8 to 60 mo). Overall median survival during the study between the groups was not different (P=0.760). No significant differences between the 2 groups were found in terms of patient demographics, short-term complications, pathologic outcomes, or tumor-node-metastasis stage. With regard to operative time, the LPD group was slightly longer than the OPD group (P<0.001). There were significant differences between groups in the time to the first passage of flatus and the time to oral intake (P<0.001). However, no differences were seen in blood loss, length of intensive care unit stay, node positive, or R0 resection between the laparoscopic and open groups.This study found that LPD is a feasible, safe, and effective method for the treatment of NPPA compared with OPD and may be a preferred method for surgeons to choose.