Background: Survival of resectable pancreas cancer (RPC) treated with resection and adjuvant therapy is 22-28 months (mo). Locally advanced unresectable pancreatic cancer (LAPC) treated with combination chemotherapy have a median survival of 24 mo. The objective of this project is to evaluate the effect of neoadjuvant treatment on survival outcome of localized PC. Methods: Charts of localized PC patients treated at Emory University from 2009 to 2016 were reviewed. Information on demographics, stage and treatment was collected. Survival rates were estimated by Kaplan-Meier method and compared with log-rank test. A Cox proportional hazard model was fitted to estimate the adjusted effect of treatment on overall survival(OS). Results: A total of 415 patients were included; 144 RPC, 158 borderline resectable (BRPC) and 108 LAPC. Stage was determined at the multidisciplinary conference. The median age was 67.7 years (30-92); 49% male, and 63% Caucasians. The median OS for RPC, BRPC, and LAPC was 16.9, 14.6 and 10.9 mo, respectively. Stage, type of chemotherapy and age were significant predictors of OS after adjusting for gender, race, age, surgery, stage, chemotherapy, margins and radiation. Of the 144 RPC, 137 underwent surgery and 3 received neoadjuvant treatment; 73 RPC were followed in outside facility with missing follow up data. Of the 71 RPC treated at Emory; 91% received adjuvant gemcitabine. Of the 158 BRPC, 84 underwent surgery; 44 received FOLFIRINOX neoadjuvant therapy, 23 received gemcitabine/nab-paclitaxel, and 16 received gemcitabine single agent. BRPC patients who underwent resection had a median OS of 18.5 mo (95%CI: 14.2, 26.4), significantly longer than RPC (P = 0.044). Combination chemotherapy was significantly associated with improved OS at 36 mo (38.9%) when compared to single agent gemcitabine (6.3% at 36 mo) (p = 0.009). BRPC patients who received FOLFORINOX and surgery had a median OS of 31.5 mo. Conclusions: Overall survival of BRPC patients who undergo resection after FOLFIRINOX is significantly improved (more than doubled) compared to upfront resection for RPC. Preoperative therapy provides the best approach for systemic disease early in the course of treatment.