OBJECTIVES Inflammatory processes (both infections and autoimmune diseases) may cause endothelial dysfunction and arterial atherosclerosis, subsequently increasing the risk of acute ischemic stroke (AIS). In this investigation, we analyzed the association between hepatitis B virus (HBV) infection and AIS risk. METHODS A Taiwan national insurance claims data set of 1,000,000 patients was used to extract 22,303 patients with HBV and 89,212 randomly selected sex- and age-matched controls from the beginning of 2000 to the end of 2006. Both groups were followed up until the appearance of AIS or the end of 2011. AIS risk was measured using the Cox proportional regression model. RESULTS After adjusting for the relevant covariates, the HBV group exhibited a lower AIS risk (adjusted hazard ratio [aHR] = 0.77, 95% confidence interval [CI]: 0.66-0.89) compared with the controls at the end of follow-up. Under the condition of no comorbidities, patients with HBV had a lower AIS risk compared with the controls (aHR = 0.65, 95% CI: 0.48-0.87). In 3 age-stratified subgroups, HBV was correlated with a significantly diminished risk of AIS (age ≤ 49 years: aHR = 0.57, 95% CI: 0.39-0.82; age 50-64 years: aHR = 0.65, 95% CI: 0.53-0.80; age ≥ 65 years: aHR = 0.96, 95% CI: 0.76-1.23). CONCLUSION HBV was correlated with a reduced risk of AIS development. Although a decrease in AIS risk was noted in the patients with HBV, preventing the development of AIS in this population warrants further attention.