Objectives We aimed to assess a novel measure of left ventricular (LV) dyssynchrony, a cardiovascular magnetic resonance-tissue synchronization index (CMR-TSI), in patients with heart failure (HF). A further aim was to determine whether CMR-TSI predicts mortality and major cardiovascular events (MCE) after cardiac resynchronization therapy (CRT). Background Cardiac dyssynchrony is a predictor of mortality in patients with HF. The unparalleled spatial resolution of CMR may render CMR-TSI a predictor of clinical benefit after CRT. Methods In substudy A, CMR-TSI was assessed in 66 patients with HF (age 60.8 ± 10.8 years, LV ejection fraction 23.9 ± 12.1% [mean ± SD]) and 20 age-matched control subjects. In substudy B, CMR-TSI was assessed in relation to clinical events in 77 patients with HF and with a QRS ≥120 ms undergoing CRT. Results In analysis A, CMR-TSI was higher in patients with HF and a QRS <120 ms (79.5 ± 31.2 ms, p = 0.0003) and in those with a QRS ≥120 ms (105.9 ± 55.8 ms, p < 0.0001) than in control subjects (21.2 ± 8.1 ms). In analysis B, a CMR-TSI ≥110 ms emerged as an independent predictor of the composite end points of death or unplanned hospitalization for MCE (hazard ratio [HR] 2.45; 95% confidence interval [CI] 1.51 to 4.34, p = 0.0002) or death from any cause or unplanned hospitalization for HF (HR 2.15; 95% CI 1.23 to 4.14, p = 0.0060) as well as death from any cause (HR: 2.6; 95% CI 1.29 to 6.73, p = 0.0061) and cardiovascular death (HR 3.82; 95% CI 1.63 to 16.5, p = 0.0007) over a mean follow-up of 764 days. Conclusions Myocardial dyssynchrony assessed by CMR-TSI is a powerful independent predictor of mortality and morbidity after CRT.