Background: Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin, a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM, has been found to have a chemo-protective role in PDAC in some in-vitro and human-based studies; conflicting literature exists regarding its potential role as a therapeutic agent. We investigated whether metformin use prior to PDAC diagnosis is associated with improved survival of patients with DM. Methods: We used the Surveillance, Epidemiology, and End-Results (SEER) linked Medicare database to identify diabetic patients with PDAC diagnosed between 2007-2011. Information regarding use of anti-hyperglycemic drugs prior to cancer diagnosis was extracted from Part D claims. The diabetic severity comorbidity index (DCSI) was used to control for DM severity. Logistic regression was used to calculate propensity scores for metformin use based on each patient’s sociodemographic characteristics, diabetic severity, and co-morbidity status. Inverse propensity weighted Cox Proportional-Hazard Models were subsequently used to assess the association between metformin use and overall survival adjusting for measured confounders. Results: We identified 1916 patients with PDAC and a diagnosis of DM on hypoglycemic medications at least one year prior to cancer diagnosis. Of these, 1098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (p < 0.01). After adjusting for confounders, patients on metformin had a 12% decreased risk of mortality compared to patients on other medications (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.81-0.96, P <.01). In stratified analysis, differences persisted for those with Charlson score 0-1 vs > 2, DCSI 0-1 vs > 2, and for those treated with insulin vs other hypoglycemic medications (p < 0.01 for all). Conclusions: Metformin is associated with increased survival among diabetics with PDAC. If confirmed in prospective study, these results suggest a possible role for metformin use in diabetics with PDAC.