The low-density lipoprotein receptor (LDLR) gene has been reported to be associated with cerebral infarction. This study aimed to explore 2 genetic LDLR variants, rs688 and rs5925, for their potential roles in cerebral infarction. This genetic association study was conducted within an isolated Taiwanese population; 815 ischemic stroke patients (431 with atherothrombotic stroke and 384 with lacunar infarction) and 430 normal controls were enrolled. There was no significant difference in the genetic frequency of rs688 and rs5925 between the control group and overall ischemic stroke, atherothrombotic stroke, or lacunar infarct groups. However, when analyzing the association between the haplotypes related to rs688 and rs5925 and cerebral ischemic stroke, the most common haplotype allele CT was used as the reference allele, and the haplotype TC associated with a 65% increased risk of overall ischemic stroke, 72% increased risk of atherothrombotic stroke, and 70% increased risk of lacunar infarction; this indicated a synergistic effect between these 2 single-nucleotide polymorphisms. The LDLR analysis based on the haplotypes rs688 and rs5925 was conducted in a Taiwanese population and provided preliminary evidence suggesting that genetic polymorphisms of LDLR are associated with cerebral infarction.