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Background: The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized controlled trial that studied 9361 adults ≥50 years of age with systolic blood pressure >130 mm Hg and ≥1 cardiovascular risk factors. Patients were randomized to intensive (≤120 mm Hg) or standard (≤140 mm Hg) systolic targets. In August 2016, a limited dataset was released for secondary analysis. We hypothesized that excessive lowering of diastolic blood pressure could cause harm. Using the data from SPRINT, we sought to determine whether the development of diastolic hypotension during treatment was associated with adverse outcomes.Methods: We included 8046 patients from SPRINT with a baseline diastolic blood pressure ≥65 mm Hg at study enrollment (4041 intensive target; 4005 standard target). Using Cox proportional hazards models, we evaluated the association between the development of diastolic hypotension (defined as ≤55 mm Hg and modeled as a time-dependent covariate) and the combined outcome of cardiovascular morbidity (myocardial infarction, other acute coronary syndromes, stroke, heart failure) and all-cause death.Results: In multivariable analyses, patients who developed diastolic hypotension had an increased risk for our primary outcome (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.24-2.26). This was true in both the intensive (HR 1.53; 95% CI, 1.04-2.26) and standard (HR 2.23; 95% CI, 1.40-3.54; P for interaction = .09) treatment arms.Conclusions: We found an association between diastolic hypotension and the combined endpoint of cardiovascular events and all-cause mortality among SPRINT participants with normal to high diastolic blood pressure at entry. Attention to diastolic blood pressure may be important for optimizing outcomes when targeting systolic blood pressure reduction. [ABSTRACT FROM AUTHOR]