AIM: To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) increase risk of pancreatic ductal adenocarcinoma (PDAC). METHODS: We recruited 585 patients with cytological and/or pathologically confirmed PDAC in National Taiwan University Hospital from September 2000 to September 2013, and 1716 age-, sex-, and race-matched controls who received a screening program in a community located in Northern Taiwan. Blood samples were tested for the presence of HCV antibodies (anti-HCV), HBV surface antigen (HBsAg), antibodies against HBsAg (anti-HBs), and hepatitis B core antigen (anti-HBc) in all cases and controls. The odds ratio (OR) of PDAC was estimated by logistic regression analysis with adjustment diabetes mellitus (DM) and smoking. RESULTS: HBsAg was positive in 73 cases (12.5%) and 213 controls (12.4%). Anti-HCV was positive in 22 cases (3.8%) and 45 controls (2.6%). Anti-HBs was positive in 338 cases (57.8%) and 1047 controls (61.0%). The estimated ORs of PDAC in multivariate analysis were as follows: DM, 2.08 (95% CI: 1.56-2.76, P < 0.001), smoking, 1.36 (95% CI: 1.02-1.80, P = 0.035), HBsAg(+)/anti-HBc(+)/anti-HBs(-), 0.89 (95% CI: 0.89-1.68, P = 0.219), HBsAg(-)/anti-HBc(+)/anti-HBs(+), 1.03 (95% CI: 0.84-1.25, P = 0.802). CONCLUSION: HBV and HCV infection are not associated with risk of PDCA after adjustment for age, sex, DM and smoking, which were independent risk factors of PDAC. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.