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Background: Neural invasion is a distinct route for the spread of pancreatic carcinoma. However, the clinicopathologic significance of neural invasion, with particular reference to intrapancreatic nerve invasion, remains to be elucidated.Methods: One hundred and fifty-three patients who underwent pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas between 2004 and 2008 were retrospectively examined. The clinical and histopathological factors, including intrapancreatic nerve invasion, were analyzed in these patients. Intrapancreatic nerve invasion (ne) were classified into 4 groups according to the following semi-quantitative scores: no invasion (ne0) seen; slight invasion (ne1) observed (1-3 points of cancer cell invasions); moderate invasion (ne2) observed (4-8 points); marked invasion (ne3) observed (>8 points) in the most extensively involved area under low power magnification (X100). The relationships between the degree of intrapancreatic nerve invasion and disease-free survival, as well as various histopathologic factors, were investigated.Results: The median disease-free survival of the 153 patients was 9 months, with a disease-free 5-year survival of 17.1%. The incidence of histological intrapancreatic nerve invasion was as follows: ne0 = 7 (5%); ne1 = 38 (25%); ne2 = 85 (56%); and ne3 = 19 (12%). There were significant differences between groups; ne0 vs ne1 (P=0.3163), ne1 vs ne2 (P=0.0007), ne0 vs ne2 (P=0.0234), ne1 vs ne3 (P=0.0000), and ne0 vs ne3 (P=0.0009) In multivariate analysis, a lack of lymph node metastases (P=0.001), incidence of intrapancreatic nerve invasion (P=0.001), and negative surgical margin (P=0.011), significantly increased the disease-free survival. The tumor stage was not associated with intrapancreatic nerve invasion. (P=0.255) However, a larger tumor size (P=0.024), a higher incidence of lymphatic invasion (P=0.036), and the presence of extrapancreatic nerve plexus invasion (P<0.001), were identified as independent factors associated with a higher incidence of intrapancreatic nerve invasion.Conclusion: Intrapancreatic nerve invasion may be useful as a predictor for recurrence after pancreaticoduodenectomy in patients with invasive ductal carcinoma of the pancreas.