Background: Filamin A and filamin B were involved in vascular development and remodeling. Herein, it is important to explore the associations of FLNAand FLNBvariants with hypertension and stroke. Methods: The associations of two single-nucleotide polymorphisms (SNPs) at FLNAand five SNPs at FLNBwith hypertension and stroke were examined in two case-control studies and a cohort study in Chinese Han population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by Logistic and Cox regression analysis respectively. In addition, filamin B, FLNAand FLNBmRNA expression were measured. Results: In the case-control study of hypertension, FLNArs2070816 (CT + TT vs. CC) and rs2070829 (CG + GG vs. CC) were significantly associated with hypertension in <55 years group (OR = 1.338, P= 0.018; OR = 1.615, P= 0.005) and FLNBrs839240 (AG + GG vs. AA) was significantly associated with hypertension in females (OR = 0.828, P= 0.041) and nonsmokers (OR = 0.829, P= 0.020). In the follow-up study, rs2070829 GG genotype carriers presented a higher risk of hypertension than CC/CG in males (HR = 1.737, P= 0.014) and smokers (HR = 1.949, P= 0.012). In the case-control study of stroke, FLNBrs1131356 variation was significantly associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH), ORsof additive model were 1.342 and 1.451, with Pvalues of 0.001 and 0.007. The FLNA transcript 2, FLNB transcript 3, transcript 4 mRNA, and filamin B expression levels were significantly different between IS cases and hypertension controls and among the genotypes of rs839240 in hypertensive individuals (P< 0.05). Conclusions: Our findings support the genetic contribution of FLNAand FLNBto hypertension, and stroke with differentially mRNA expression.