High blood pressure has been the second most important determinant of disease burden in Iran since the 1990s. Despite well-recognized evidence on the association of high blood pressure and mortality in other countries, this relationship has not been fully investigated in the demographic setting of Iran. The current study is the first large-scale longitudinal study of this association in Iran. Briefly, 50 045 subjects between 40 and 75 years of age have been recruited and followed. Blood pressure measurements were carried out at baseline. Causes of death were reported and verified by verbal autopsy throughout the follow-up period. The outcomes of interest were all-cause deaths and deaths due to ischemic heart disease (IHD) or stroke. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). A total of 46 674 subjects free from cardiovascular disease at baseline were analyzed. Absolute mortality rates increased along with increasing systolic or diastolic blood pressure above 120 and 80 mm Hg, respectively. Adjusted HRs (95% confidence intervals) for each 20 mm Hg increase in systolic blood pressure in all age groups were 1.18 (1.13-1.23) for all-cause mortality, 1.21 (1.13-1.31) for deaths due to IHD and 1.50 (1.39-1.63) for deaths due to stroke. Unadjusted and adjusted HRs were higher in younger subjects and decreased with increasing age of the participants. High blood pressure is a serious threat to the health of Iranians. The entire health-care system of Iran should be involved in a comprehensive action plan for controlling blood pressure.