The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene has been associated with stroke. The majority of the reported ALOX5AP associations have considered non-radiologically confirmed infarcts as the stroke phenotype. We assessed the association of genetic variants in ALOX5AP with stroke defined by the presence of infarcts on brain magnetic resonance imaging (MRI). We studied 202 persons with MRI-defined brain infarcts and 487 healthy individuals of Caribbean Hispanic ancestry. Another sample of European ancestry comprised 1823 persons with MRI-defined brain infarct and 7578 control subjects. Subjects were genotyped for the 4 single nucleotide polymorphisms (SNPs) that define ALOX5AP HapA haplotype. No association was found between SNPs and MRI-defined brain infarcts. Our data do not support the hypothesis that variants in ALOX5AP are associated with risk of MRI-defined brain infarcts.