It was shown that improvement in left ventricular (LV) function and reverse remodeling after cardiac resynchronization therapy (CRT) were greater in patients with nonischemic cardiomyopathy than in those with ischemic cardiomyopathy. The aim of this study is to evaluate the influence of scar burden on response to CRT. We included 34 patients with ischemic cardiomyopathy (New York Heart Association class 3.1 +/- 0.4, LV ejection fraction 23 +/- 7%). Contrast-enhanced magnetic resonance imaging was used to determine total scar burden, using a 17-segment model with a 5-point hyperenhancement scale (from score 0 = no hyperenhancement, indicating no scar, to score 4 = hyperenhancement >76%, transmural scar). Linear regression analysis showed a significant correlation (r = -0.91, p <0.05) between total scar burden at baseline and change in LV end-systolic volume after 6 months of CRT. Also, patients not responding to CRT had significantly more scar tissue than responders. A scar burden >1.20 resulted in complete functional nonresponse. In conclusion, total scar burden, assessed using contrast-enhanced magnetic resonance imaging, is an important factor influencing response to CRT and may be included in the selection process for CRT candidates.