606 Background: Standard of care for early-stage resectable pancreatic cancer (PC) includes a combination of surgical resection and chemotherapy. Frequently, CA 19-9 is used as a biomarker to monitor treatment effect and has prognostic significance. We evaluated the impact of CA 19-9 on overall survival (OS) in patients with clinical stage I PC (cT1N0 and cT2N0) utilizing the National Cancer Database (NCDB). Methods: The NCDB was queried between 2010 and 2014 to identify patients with clinical stage I PC. Patients who had missing or undocumented CA 19-9 value at diagnosis were excluded. Demographic and clinical characteristics were analyzed. Patients were stratified into two cohorts based on the CA 19-9 value at diagnosis – CA 19-9 < 98 U/mL and CA 19-9 > 98 U/mL. Univariable and multivariable analyses were performed, and variables associated with OS were identified. Kaplan-Meier survival curves were computed to compare the OS between the two cohorts. Results: A total of 12,480 patients met our inclusion criteria. A majority of patients were female (51.9%), white (84.4%), with a median age of 70 years. Nearly, half the patients received care in an academic/research program (49.5%). A majority of patients had tumors located in the head of the pancreas (71.9%), and received single-agent (35.1%) or multiagent (22.9%) chemotherapy. Over half the patients (6505 patients, 52.1%) had a CA 19-9 value > 98 U/mL. A CA 19-9 value > 98 U/mL in patients predicted a significantly shorter median OS of 12.1 months compared to 19.4 months in patients with a CA 19-9 < 98 U/mL, p<0.0001 (Table). The 5-year OS rate was 9.9% in patients with a CA 19-9 value of > 98 U/mL compared to a 5-year OS rate of 18.1% for patients with a CA 19-9 value < 98 U/mL. On multivariable analysis, CA 19-9 > 98 compared to CA 19-9 < 98 (HR 1.53, p<0.001) and black race compared to white race (HR 1.10, p<0.001) was associated with worse survival, whereas tumor location in the body and tail compared to the head (HR 0.82, p<0.001), single-agent (HR 0.55, p<0.001) and multiagent (HR 0.55, p<0.001) chemotherapy compared to no chemotherapy, independently predicted improved OS. Conclusions: This is the first National Cancer Database study to demonstrate the prognostic value of CA 19-9 in patients with clinical stage I pancreatic cancer, with a value < 98 U/mL predicting improved survival. Clinical stage I pancreatic cancer patients appear to derive a significant benefit from chemotherapy, including single and multiagent chemotherapy, irrespective of the CA 19-9 value.[Table: see text]