Angiopoietin-2 is an important mediator of angiogenesis, and we hypothesized that genetic variants of ANGPT2 (the gene encoding angiopoietin-2) would result in abnormal angiogenesis and contribute to stroke susceptibility. To test our hypothesis, we investigated the association of variants in the promoter of ANGPT2 with stroke in a multi-centre case-control study. We found that the C allele of rs3739390 conferred a 1.42-fold risk of lacunar infarction {adjusted OR (odds ratio), 1.42 [95% CI (confidence interval), 1.08-1.87]; P=0.012} and a 2.10-fold higher transcriptional activity than did the corresponding G allele rs3739390G. The haplotype G-G-T conferred a 1.54-fold risk of atherothrombotic stroke and a 1.64-fold risk for haemorrhagic stroke, whereas the haplotype G-C-C conferred approx. a 2.0-fold risk of each subtype of stroke. In conclusion, our results indicate that haplotypes in the promoter of ANGPT2 confer a high risk of stroke in a Chinese population.