Abstract Background: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism. The Ser447Ter mutation of LPL may be associated with ischemic cerebrovascular diseases. We investigated whether the LPL variants were related to risk of strokes in Chinese Hans. Methods: We recruited 160 patients with cerebrovascular diseases (ischemic stroke, n=96; hemorrhagic stroke, n=64) and 117 age-matched controls. All subjects were Chinese Hans. Subjects were analyzed for the Ser447Ter mutation by restriction fragment length polymorphisms of the LPL gene. Results: As compared with controls, the frequency of LPL genotype CG (heterozygous Ser447Ter mutation) was lower in ischemic stroke patients (10.4% vs. 21.4%, p<0.05), and was not significantly different in hemorrhagic stroke patients (15.6% vs. 21.4%, p>0.05). The LPL G allele frequency was also lower in ischemic stroke patients (5.2%) vs. controls (10.7%, p<0.05). There was no difference between hemorrhagic stroke patients (7.8%) and controls. Serum Lp(a) concentrations were markedly lower in CG carriers than that in CC carriers in both stroke patients and the controls ( p<0.05). There was no significant difference in the concentrations of other lipids. Conclusions: Patients with ischemic stroke have a lower frequency of the LPL Ser447Ter mutation, which indicates that this mutation may have protective effect on ischemic stroke.