High blood pressure (BP) has been well established as a leading risk factor for both cardiovascular disease and mortality in general. However, the effect of long-term exposure to elevated BP on mortality risks in Asian populations remains unclear. The purpose of this study was to investigate the effects of time-averaged BP levels over 5 years on subsequent cardiovascular disease mortalities in a Japanese population. A total of 46 484 adults (14 771 men and 31 713 women) aged 40-79 years, who had no history of stroke or heart disease and who underwent health checkups in Ibaraki prefecture, Japan, in 1993 and 1998 were followed up through 2005. Hazard ratios (HRs) for mortality were estimated using a Cox proportional hazard model. Multivariate HRs (95% confidence interval) associated with a 10 mm Hg increase in systolic BP were measured in 1993 and 1998, and their averages were 1.11 (1.05-1.16), 1.13 (1.07-1.18) and 1.17 (1.10-1.27), respectively. Multivariate HRs for a 10 mm Hg increase in time-averaged systolic BP were 1.12 (1.03-1.21) in men and 1.24 (1.13-1.35) in women. The subgroup analysis of antihypertensive use showed that multivariate HRs for time-averaged systolic BP were 1.20 (1.11-1.29) in sustained non-users and 1.17 (1.04-1.32) in sustained users. Similar results were also obtained for diastolic BP. In conclusion, long-term exposure to elevated BP substantially associates with excess risk for cardiovascular disease mortality among Japanese subjects, irrespective of antihypertensive medication use. Thus, appropriate management of BP is important in both users and non-users of antihypertensive medication. Keywords: antihypertensive medication use; cardiovascular disease; mortality; prospective cohort study; time-averaged blood pressure INTRODUCTION Elevated blood pressure (BP) is one of the major risk factors for mortality from cardiovascular disease (CVD) and all-cause comorbidity worldwide. [1][2][3][4] The excess risk for CVD and all-cause mortalities was substantially attributed to hypertension when compared with normal BP levels. 3 Therefore, management of hypertension is of utmost importance, not only in clinical practice but also in public health practice.Atherosclerotic vascular disease evolves slowly and is undoubtedly related to the cumulative exposure of individuals to CVD risk factors over a lifetime. 5 High BP is a typical example of such a lifelong exposure. Consequently, previous investigations analyzing the relationship of BP to CVD mortality risk might be limited by a failure to effectively characterize or adequately quantify long-term vascular exposure. Some previous investigations have highlighted the importance of BP levels over time on incidence risk for CVD. The