The aim of this study was to clarify whether the apolipoprotein E gene (APOE) is related to ischemic stroke subtypes in Taiwan's Chinese population. Using the classification of Cerebrovascular Diseases III, 143 patients with lacunar infarction, 114 patients with atherothrombotic infarction, and 112 healthy controls were enrolled. APOE genotype was determined using polymerase chain reaction. Regarding the distribution of APOE genotypes, the frequency of epsilon3/epsilon4 genotypes in lacunar patients was significantly different from that in control subjects, by logistic regression, using epsilon3/epsilon3 as a reference group. There was no significant difference between atherothrombotic patients and the control group in the distribution of APOE genotypes or alleles. The present finding suggests that there is a probable association between epsilon3/epsilon4 genotype and lacunar infarcts, but not atherothrombotic infarcts. This indicates that genetic factors may play a role, at least partially, in lacunar infarction in Taiwan's Chinese population.