315 Background: Novel biomarkers to predict outcomes in pancreatic adenocarcinoma (PDA) are urgently needed. Complement activation, an important mediator of inflammatory processes, has been reported in some solid tumors but its role in PDA is unknown. We evaluated the prognostic role of complement in a prospective cohort of PDA patients. Methods: Blood samples were collected from consenting PDA patients at study entry (prior toany new regimen) in a prospective biorepository protocol at Cleveland Clinic from 2013-2016. Samples were processed for C3a, C4a, and C5a levels using ELISA on serum samples (BD Biosciences). Data on clinical variables, treatment, and survival were collected from medical records. Resectability was defined using Intergroup criteria. Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) are presented. Results: The study population comprised 48 consecutive patients. Median age was 65 years (range, 41-84); 60% (n=29) were female; 33 (69%) had potentially curable (resectable or borderline resectable) disease. Overall, 43 (93%) received chemotherapy; 22 (46%) received radiation; 29 (60%) underwent surgery. Median follow-up was 17 months. Median OS was 10.9 (1.6-54.5) months. Baseline levels, and associations with stage and OS are shown in Table. Increasing levels of C3a, C4a and C5a were associated with worsened survival (HR 1.00-1.03 per each unit increase in baseline level) despite not being significantly associated with stage. Conclusions: Levels of C3a, C4a, and C5a are detected in nearly all patients with PDA. Increased levels correlate with OS. Complement activation has not been reported previously in PDA and may be a potential therapeutic target. Our findings suggest that complement levels may serve as novel biomarkers. [Table: see text]