Background: The efficacy and tolerability of intensive blood-pressure lowering may vary by pulse pressure (systolic minus diastolic blood pressure). Methods: SPRINT randomized 9361 high-risk adults without diabetes and who were ≥50 years with systolic blood pressure 130-180 mm Hg to intensive or standard antihypertensive treatment. The primary efficacy end point was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety end point was composite serious adverse events. We examined the prognostic implications of baseline pulse pressure and the effects of intensive blood-pressure lowering on clinical outcomes across the spectrum of pulse-pressure values using restricted cubic splines. Results: Mean baseline pulse pressure was similar between the 2 study groups (intensive treatment 61±14 mm Hg vs standard treatment 62±14 mm Hg; P = 0.59). Except stroke, for which the association with pulse pressure was best defined as linear, pulse pressure displayed a nonlinear U-shaped relationship with the risk of all tested clinical end points (P <0.05), though no association remained significant upon multivariable adjustment (P >0.05). The benefit of intensive blood-pressure management on mortality appeared greatest in patients with a pulse pressure ∼60 mm Hg (P = 0.03 for interaction). Pulse pressure did not modify the effect of intensive blood-pressure lowering for other clinical end points (P >0.05 for interaction). Conclusion: In a large randomized clinical trial of patients with a high risk of cardiovascular events, risks and benefits of intensive blood-pressure lowering did not appear to be modified by baseline pulse pressure. Selection of appropriate candidates for intensive blood-pressure lowering should not be limited by this parameter.