Overseas guidelines to manage hypertension recommend selecting different drugs depending on age, but no studies have investigated the relationship between drug selection and age-and sex-related differences, although such information may help to reduce the risk of cardiovascular mortality. The Azilsartan Circadian and Sleep Pressure--the First Study (ACS1) trial was a multicentered, randomized, open-label, two-parallel group study comparing the effects of an angiotensin II receptor blocker (azilsartan) and a calcium channel blocker (amlodipine). The present study is a post hoc analysis of ACS1 to investigate age-and sexrelated differences in the antihypertensive effects between azilsartan and amlodipine. Azilsartan significantly reduced diastolic blood pressure in male patients younger than 60 years compared with amlodipine, but amlodipine significantly reduced systolic blood pressure in female patients 60 years and older compared with azilsartan. A randomized controlled trial to evaluate cardiovascular outcomes will demonstrate whether a diastolic blood pressure-lowering effect with azilsartan is significantly effective in male patients younger than 60 years. J Clin Hypertens (Greenwich). 2016;18:672-678. ª 2016 Wiley Periodicals, Inc.For the treatment of hypertension to decrease the risk of cardiovascular events, the Eighth Joint National Committee (JNC 8) recommends target blood pressure (BP) goals of <150/90 mm Hg for persons 60 years and older and a BP goal of <140/90 mm Hg for those younger than 60 years.1 Although the American Society of Hypertension (ASH) and the International Society of Hypertension (ISH) guidelines recommend a target BP goal <140/90 mm Hg regardless of age, as for drug selection, an angiotensin II receptor blocker (ARB) or angiotensin-converting enzyme inhibitor is recommended as the first-line drug in patients younger than 60 years, while a calcium channel blocker (CCB) or thiazide diuretic is recommended in patients 60 years and older.2 The 2014 Japanese Society of Hypertension (JSH) guidelines, however, recommend a target BP goal of 140/90 mm Hg for all ages. 3 It has recently been reported that regarding the relationship between cardiovascular events and diastolic BP (DBP) and systolic BP (SBP), one standard deviation (SD) increase (13.5 mm Hg) in SBP raises the risk of total mortality (hazard ratio [HR], 1.19; 95% confideince interval [CI], 1.08-1.30]) and cardiovascular mortality (HR, 1.51; 95% CI, 1.34-1.70) in patients of 50 years and older. In patients younger than 50 years, however, one SD increase (8.2 mm Hg) in DBP, not SBP, raises the risk of total mortality (HR, 2.05; 95% CI, 1.26-3.33) and cardiovascular mortality (HR, 4.07; 95% CI, 1.60-10.4). 4 Another study on the relationship between DBP/SBP and cardiovascular events in patients younger than 50 years also reported that only SBP is associated with an increased risk of cardiovascular mortality in women, while both SBP and DBP are associated with a higher risk of cardiovascular mortality, independent of each other, in me...