Background: Lymph node (LN) metastasis is a significant prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). However, little is known about the significance of direct LN invasion by the tumorAim: Our aim is to investigate whether direct LN invasion has the same prognostic significance as regional LN involvementMethods: Retrospective review of clinicopathologic data of patients with PDAC between 1/1993 and 7/2008. “Direct” is defined as LNs involved through direct extension of the tumor and “regional” as all other LNs in the resected specimenResults: Overall 533 patients were resected for PDAC of whom 173 had 0 +LNs, 91 had 1 +LN (direct:25, regional:66), 79 had 2 +LNs (direct:6, regional:68, both patterns:5) and 190 had >2 +LNs. The sex and age distribution of patients with directly invaded LNs, +regional LNs and -LNs were similar (females:58%, 46% and 52% (p=0.3), age:67yrs, 67yrs and 68yrs (p=0.9) respectively). Negative LN disease was a significant predictor of survival (N0:28mo, N1:18mo; p=0.003). Overall survival of patients with directly invaded LNs was not significantly different from patients with +regional LNs (direct:15mo, regional:22mo; p=0.6 for patients with 1 +LN and direct:18mo, regional:12mo; p=0.5 for patients with 2 +LNs). Patients with 1 +LN had better survival relative to patients with 2 +LNs and patients with >2 +LNs (21.4mo, 13.9mo and 13.4mo respectively; p=0.001)Conclusions: For patients with PDAC node positivity is a significant predictor of overall survival. Node positivity rather than the mechanism of node involvement is significant. Prognosis is worse when more than one LN is involved