Low pulse pressure (PP) is associated with poor outcome in hospitalized patients with systolic heart failure (HF). However, the relation between PP and response to cardiac resynchronization therapy with defibrillator (CRT-D) is unknown. We aimed to evaluate the relation between preimplantation PP and echocardiographic response to CRT-D and subsequent clinical outcome after 1 year. The relation between preimplantation PP and echocardiographic response to CRT-D (defined as >15% reduction in left ventricular (LV) end-systolic volume at 1 year) was evaluated in 754 patients with CRT-D with left bundle branch block enrolled in Multicenter Automatic Defibrillator Cardioverter Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. The association between PP at 1 year and the risk for subsequent HF or death was evaluated using multivariate Cox model. Patients with high versus low PP (>40 vs 40 mm Hg [lower quartile]) had a significantly greater reduction in LV end-systolic volume, LV end-diastolic volume, and LV dyssynchrony (p 0.01 for all comparisons). In multivariate analysis, the presence of high PP was associated with a 3.5-fold (p 0.001) increase in the likelihood of a positive echocardiographic response to CRT-D. Patients with high PP (40 mm Hg, lower quartile) 1 year after CRT-D implantation experienced a 50% reduction in the risk of subsequent HF or death (p = 0.001) and 63% reduction in death only (p = 0.001), compared with patients with low PP. In conclusion, high baseline PP is an independent predictor of echocardiographic response to CRT-D, and high PP after device implantation is associated with improved subsequent clinical outcome.