We sought to determine whether correction of mechanical left ventricular (LV) dyssynchrony as defined by tissue Doppler imaging (TDI) is predictive for transplant-free long-term survival in patients (pts.) undergoing cardiac resynchronization therapy (CRT). In 76 CRT recipients TDI curves from the septal, lateral, anterior, and inferior basal LV were obtained at baseline and after 6 ± 4 months. A time difference between regional electromechanical delays (EMD) of ≥40 ms was considered dyssynchronous. At follow-up, pts. were classified as TDI-responders (TDI-R: dyssynchrony at baseline, corrected by CRT) versus non-responders (TDI-NR: either not dyssynchronous at baseline, or persisting dyssynchrony). Pts. were then followed by standard echocardiography over 21 ± 6 months and were re-classified as LV remodelers (LV-R: LV volume reduction of >10%) versus non-remodelers (LV-NR). The end-point during clinical long-term follow-up of 65 ± 38 months was all-cause mortality or heart transplantation. 44 out of the 76 pts. (58%) were classified as TDI-R, 32 (42%) as TDI-NR. Significant reverse LV remodeling was observed in 41 (54%) pts., while 35 (46%) did not improve LV size and function. TDI-R was associated with LV-R in 35 pts. (85%; P < 0.001). During long-term follow-up, 38 pts. (50%) reached the end point, 11 (30%) in the TDI-R group, and 27 (70%) in the TDI-NR group (P < 0.0003). Mechanical resynchronization as defined by TDI translates into a significant survival benefit in CRT recipients.