We performed a meta-analysis in an effort to systematically explore the association between apolipoprotein E (ApoE) epsilon2/epsilon3/epsilon4 polymorphisms and hypertension. We searched for case-control studies in English-language publications performed with human subjects using MEDLINE and included appropriate studies that had been published as of 6 May 2009. Fixed-effects models were used to pool data when between-study heterogeneity was absent, and random-effects models were used otherwise. Data and study quality were assessed in duplicate. Publication bias was assessed by calculating the fail-safe number. From six heterogeneous studies that included a total of 1812 patients with hypertension and 1762 controls, we found that the ApoE epsilon4 allele was significantly associated with hypertension using a random-effects model (odds ratio (OR)=1.79; 95% confidence interval (CI): 1.04 to 1.19; P=0.04). With regard to ApoE genotypes, we observed that the association with hypertension was more prominent when ApoE4/4 was compared with E3/3, with a nearly twofold increased risk identified for the ApoE4/4 genotype using a random-effects model (OR=1.97; 95% CI: 1.11 to 3.52; P=0.02). Furthermore, after restricting our analysis to Asian populations, the contrasts between the risk of hypertension among individuals possessing ApoE epsilon4 vs. epsilon3 and ApoE4/4 vs. ApoE3/3 were positively reinforced, with ORs of 1.97 (95% CI, 0.93 to 4.15; P=0.08) and 2.27 (95% CI, 1.03 to 4.98; P=0.04), respectively. The fail-safe number supported these significant associations at a significance level of 0.05. Taken together, our meta-analysis expands the data available regarding genetic risk factors for hypertension by illustrating that the presence of the ApoE epsilon4 allele is associated with an increased risk of developing hypertension and that it appears to be recessive. Of note, this effect was more pronounced in Asians.