Abstract Background Cardiac resynchronization therapy (CRT) has been shown to improve heart failure (HF) symptoms and survival. We hypothesized that a greater improvement in left-ventricular ejection fraction (LVEF) after CRT is associated with greater survival benefit. Methods and Results In 693 patients across 2 international centers, the improvement in LVEF after CRT was determined. Patients were grouped as non-/modest-, moderate-, or super-responders to CRT, defined as an absolute change in LVEF of ≤5%, 6–15%, and >15%, respectively. Changes in New York Heart Association (NYHA) functional class and left ventricular end-diastolic dimension (LVEDD) were assessed for each group. There were 395 non-/modest-, 186 moderate-, and 112 super-responders. Super-responders were more likely to be female and to have nonischemic cardiomyopathy, lower creatinine, and lower pulmonary artery systolic pressure than non-/modest- and moderate-responders. Super-responders were also more likely to have lower LVEF than non-/modest-responders. There was no difference in NYHA functional class, mitral regurgitation grade, or tricuspid regurgitation grade between groups. Improvement in NYHA functional class (−0.9 ± 0.9 vs −0.4 ± 0.8 P  < .001 and −0.6 ± 0.8 P  = .02) and LVEDD (−8.7 ± 9.9 mm vs −0.5 ± 5.0 and −2.4 ± 5.8 mm P  < .001 for both) was greatest in super-responders. Kaplan-Meier survival analysis revealed that super-responders achieved better survival compared with non-/modest- ( P  < .001) and moderate-responders ( P  = .049). Conclusions Improvement in HF symptoms and survival after CRT is proportionate to the degree of improvement in LV systolic function. Super-response is more likely in women, those with nonischemic substrate, and those with lower pulmonary artery systolic pressure.