BACKGROUND: There is considerable interest in a neoadjuvant approach for resectable pancreatic ductal adenocarcinoma (PDAC). This study evaluated perioperative gemcitabine + erlotinib (G+E) for resectable PDAC. METHODS: A multicenter, cooperative group, single-arm phase II trial was conducted between April 2009 and November 2013 (ACOSOG Z5041). Patients with biopsy-confirmed PDAC in the pancreatic head without evidence of involvement of major mesenteric vessels (resectable) were eligible. Patients (n=123) received an eight-week cycle of G+E before and after surgery. The primary endpoint was two-year overall survival (OS), and secondary endpoints included toxicity, response, resection rate, and time to progression. Resectability was assessed retrospectively by central review. The study closed early due to slow accrual; no formal hypothesis testing was performed. RESULTS: One hundred fourteen patients were eligible, consented, and initiated protocol treatment. By central radiologic review, 97 (85%) of the 114 patients met protocol resectability criteria. Grade 3+ toxicity was reported in 60% and 79% of patients during the neoadjuvant phase and overall, respectively. Twenty-two of 114 (19%) patients did not proceed to surgery, 83 patients (73%) were successfully resected. R0 and R1 margins were obtained in 67 (81%) and 16 (19%) resected patients, respectively. Fifty-four patients completed postoperative G+E (65%). The two-year OS rate for the entire cohort (n=114) was 40% (95%CI 31–50) with a median OS of 21.3 months (95%CI 17.2–25.9). The two-year OS for resected patients (n=83) was 52% (95%CI 41–63) with a median OS of 25.4 months (95%CI 21.8–29.6). CONCLUSIONS: For resectable PDAC, perioperative G+E is feasible. Further evaluation of neoadjuvant strategies in resectable PDAC is warranted with more active systemic regimens.