BACKGROUND: Current preoperative risk stratification modalities for pancreatic ductal adenocarcinoma (PDA) patients are inadequate. Elevated serum matrix metalloproteinase 7 (MMP7) is associated with metastatic PDA. We evaluated preoperative MMP7 level as a prognostic marker in patients with resectable PDA. METHODS: From a prospectively maintained database, we identified PDA patients who underwent operation with curative intent from 2004 to 2008 and had serum collected preoperatively. MMP7 was measured by enzyme-linked immunosorbent assay. Patients were defined as having advanced disease if they were found to be unresectable at the time of operation or had nodal involvement on final pathology. RESULTS: Preoperative serum samples were available for 134 patients. Using a cutoff of 13.5 ng/mL, MMP7 was highly predictive for advanced disease. For patients who underwent R0 resection, MMP7 > 13.5 ng/mL was strongly associated with N1 status, T3/T4 stage, moderate/poor differentiation, and perineural invasion. The median recurrence-free survival was 5.0 months in patients with MMP7 > 13.5 ng/mL versus 9.9 months for patients with lower values (P = 0.004). CONCLUSIONS: Very elevated serum MMP7 was highly predictive of unresectable disease and nodal involvement despite favorable preoperative cross-sectional imaging. MMP7 should be further evaluated as a biomarker to risk-stratify PDA patients prior to operation.