Objective To evaluate the effect of pathological portal vein (PV)/superior mesenteric vein (SMV) invasion during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma and the clinical significance of PD with PV/SMV resection in patients without pathological evidence of venous invasion.Methods From January 1, 2013 to December 31, 2017, data of 183 patients who had PD for pancreatic adenocarcinoma were collected. Eighty-one patients had PD with PV/SMV resection for pancreatic adenocarcinoma, among them, 42 cases (51.9%) had pathological pathological PV/SMV invasion (P/S+ group) and 39 patients (48.1%) didn’t have pathological PV/SMV invasion (P/S− group). One hundred and two patients had a standard PD without PV/SMV resection (control group). Multivariate analysis was used to identify predictive variables which influencing survival and the Kaplan-Meier method to estimate patients’ survival.Results There were no differences in gender, age, preoperative CA19-9 level, type of operation, resection margin status, tumor differentiation, tumor size, tumor TNM stage, perineural invasion, lymph node status, lymph node ratio, blood loss and use of adjuvant chemotherapy (P>0.05). And moreover, no significant differences were found between the PD combined PV/SMV resection group and the control group in morbidity, mortality, reoperation (P>0.05). Univariate analysis revealed a significant difference in overall survival (OS) between the P/S+ group, P/S– group and control group (P<0.001), median survival time were 10 months, 19 months and 20 months, respectivly. Moreover, depth of PV/SMV invasion, use of adjuvant chemotherapy and tumor differentiation were independent prognostic factors by multivariate survival analysis.Conclusions OS of patients with PV/SMV invasion is significantly worse than that of patients without PV/SMV invasion, no matter underwent PV/SMV resection or not. The cause of that maybe invasion to the tunica intima by tumor limits OS of patients with pancreatic adenocarcinoma. OS of PV/SMV-resected patients without pathological PV/SMV invasion is similar to that of patients who had standard PD without PV/SMV resection. Whether the patients can benefit from routine resection of PV/SMV is still controversial.