We examined the influence of the Q89R variant in low-density lipoprotein receptor-related protein 5 on hypertension in a large Japanese cohort. We used multivariate logistic regression analysis to adjust for the effects of other factors known to influence hypertension such as age, body mass index, blood chemistry and lifestyle. Our cohort consisted of 1444 males and 1161 females selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as systolic blood pressure 140 mmHg and/or diastolic blood pressure 90 mmHg or the use of antihypertensive medication. Because the RR genotype was so rare (three normotensive males and three normotensive females), they were excluded from analyses. Genotype distributions for Q89R in hypertensive females (QR = 14, QQ = 60) were significantly different (p = 0.033) from normotensive females (QR = 113, QQ = 971). In contrast, those in hypertensive males (QR = 26, QQ = 230) and in normotensive males (QR = 145, QQ = 1040) were similar. Allele distributions were not significantly different in either gender. In females, multivariate logistic regression showed that the QR genotype was associated with hypertension with odds ratio of 2.1 compared to the QQ genotype. This study indicates that the Q89R polymorphism is an independent factor for hypertension in Japanese females.