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SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated the benefit of achieving strict blood pressure control with a lower target blood pressure level in high-risk patients with hypertension. The aim of this post hoc analysis was to investigate the relationship between the 2-year average on-treatment home blood pressure and cardiovascular disease risk in subgroups stratified by risk status using data from the HONEST study (Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure). Participants in the HONEST study (n=21 591) were stratified according to risk level as follows: SPRINT population (n=5823)-patients (≥50 years of age) without diabetes mellitus or prior stroke, with SPRINT-defined cardiovascular risk and systolic blood pressure (SBP) of ≥130 mm Hg; SPRINT-excluded high-risk population (n=5481)-patients with diabetes mellitus or prior stroke; and non-SPRINT low-risk population-all other patients in the HONEST study (n=10 287). Cardiovascular disease event risk was 6.32 events per 1000 person-years in the SPRINT population, which was higher than in the non-SPRINT low-risk (3.39; P<0.001) and lower than the SPRINT-excluded high-risk (12.41; P<0.001) populations. In the SPRINT and the SPRINT-excluded high-risk populations, a lower home SBP achieved was associated with lower cardiovascular disease risk, with the lowest risk in patients with a home SBP <125 mm Hg. The non-SPRINT low-risk population showed a J-curve association between on-treatment home SBP and cardiovascular disease risk with the lowest risk at a home SBP of 135 to <145 mm Hg. Intensive therapy targeting home SBP of <125 mm Hg would be beneficial for high-risk hypertensive patients. Clinical Trial Registration- URL: http://www.umin.ac.jp/ctr/index.htm . UMIN Clinical Trials Registry, trial no.: UMIN000002567.