Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of US cancer related deaths. This study assessed the oncologic benefit of a neoadjuvant chemotherapy (NAC) treatment strategy for patients with clinical Stage I/II PDAC. Methods: Patients with biopsy confirmed PDAC and clinical Stage I/II disease were treated with a protocol of NAC. The primary study endpoint was median overall survival (OS). Kaplan-Meier survival curves were compared using the log-rank test. Results: 56 patients met inclusion criteria. Of these, 21 patients (38%) had Stage I disease and 35 (62%) had Stage II disease. The median OS for the entire study population was 18.7 months. A total of 22 (39%) patients were managed with NAC+S; 34 (61%) received NAC alone. Median OS and 2-year survival rates were greater in those completing NAC+S compared to NAC alone (median OS 28.8 months vs. 17.3 months: p=0.05; 2-year OS: 55% vs 21%: p=0.01) . Interestingly, patients managed with NAC who were not candidates for surgical resection after restaging demonstrated a survival advantage (17.3 months) compared to what was previously reported in historical controls. Conclusion: NAC+S provided a significant 11.5 month improvement in median OS compared to treatment with NAC alone. Modern NAC may contribute a significant oncologic benefit in the overall treatment strategy for patients with Stage I/II PDAC, even if surgery is not ultimately pursued.