BACKGROUND: Some patients operated by pancreaticoduodenectomy for resectable pancreatic head adenocarcinoma will present with a recurrence during the first year (early recurrence). OBJECTIVE: The aim of this study was to determine prognostic factors associated with early recurrence in a large retrospective study. METHODS: From January 1995 to November 2010, all patients operated by pancreaticoduodenectomy for pancreatic head adenocarcinoma in our institution were retrospectively included. Univariate and multivariate analyses were performed to determine factors associated with early recurrence. RESULTS: A total of 166 patients were included; 57 patients (34%) developed early recurrence. In univariate analysis, factors associated with early recurrence were perineural invasion (p = 0.0002), preoperative bilirubin (p = 0.01), lymph node ratio (LNR) ≥0.2 (p = 0.009), and T stage (p = 0.02). In multivariate analysis, perineural invasion (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.42-7.72; p = 0.005), LNR ≥0.2 (OR 2.55; 95% CI 1.17-5.52; p = 0.02), and preoperative bilirubin (OR 1.04; 95% CI 1.01-1.07; p = 0.03) were independent factors associated with early recurrence. Perineural invasion was also associated with poor overall survival (p = 0.001) and poor disease-free survival (p = 0.07). CONCLUSION: In our study, perineural invasion (OR 3.31) is more accurate than T stage and lymph node status (OR 2.55) to predict early recurrence after pancreatoduodenectomy for pancreatic head adenocarcinoma