Although vascular invasion is a well-established indicator of poor prognosis for patients with infiltrating ductal adenocarcinoma of the pancreas (PDAC), the histopathologic characteristics of vascular invasion are not well described. Hematoxylin and eosin-stained slides from 209 surgically resected infiltrating PDACs were systematically evaluated for the presence or absence of microscopic vascular invasion. For the cases with vascular invasion, we further categorized the histologic pattern of invasion into conventional and pancreatic intraepithelial neoplasia-like (PanIN-like). In addition, several histopathologic factors in the surrounding blood vessels, including lymphocytic infiltration and luminal fibrosis, were carefully assessed. Data were compared with clinicopathologic variables, including patient survival. Microscopic vascular invasion was observed in 136 of the 209 PDACs (65.1%). Vascular invasion mimicking pancreatic intraepithelial neoplasia (PanIN-like invasion) was observed in 94 of the 136 cases (69.1%) with vascular invasion. Microscopic vascular invasion was associated with increased tumor size (P=0.04), higher pT classification (P=0.003), lymph node metastasis (P<0.0001), and perineural invasion (P=0.005). Vascular invasion was inversely correlated with neo-adjuvant therapy (P<0.0001). Examination of adjacent blood vessels revealed that peritumoral blood vessels with intimal lymphocytes (P=0.002), intimal (P=0.007) and medial (P=0.001) fibrosis, and cancer cells in vascular wall (P<0.0001) were all highly associated with the intraluminal vascular invasion. In univariate analysis, patients whose cancers had microscopic vascular invasion (median survival, 15.3 mo) had a significantly worse survival than did patients with carcinomas without vascular invasion (25.1 mo; P=0.01, log-rank test). Microscopic vascular invasion is a poor prognostic indicator and can histologically mimic PanIN.