To investigate the genetic association between the ryanodine receptor-3 (RYR-1) gene polymorphism of patients with hypertension and large artery atherosclerosis (LAA) in the Han descent population in Northern China. Methods:Total 232 patients experiencing hypertension and LAA-related stroke were recruited to participate in the study as the stroke group. Two hundred hyperpietic patients without cervical artery stenosis were recruited as the hypertension group. Two hundred healthy physical examination patients without hypertension from our hospital physical examination centre were selected as the control group. Genotype was determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry for the polymorphism of the RYR-3 gene. The genotype frequencies of the RYR-3 gene among groups were analyzed. Results: There was no significant difference in the frequencies of genotype and allele of RYR-3 gene rs877087 between the stroke group and the hypertension group (both P＞0.05). However, there was a significant difference between the stroke group and the control group (both P＜0.05). There was a significant difference in the frequencies of genotype and allele of RYR-3 gene rs2229116 between the stroke group and the hypertension group (both P＜0.05). For patients with hypertension, multivariate logistic regression analysis showed that polymorphism of RYR-3 gene rs2229116 (OR=1.155, 95％CI 1.018~1.626, P=0.030) was a risk factor for LAA-related stroke. Conclu? sion: In patients with hypertension, polymorphism of RYR-3 gene rs2229116 may be closely linked to large artery atherosclerosis-related stroke.