Introduction: The cardiac resynchronization therapy (CRT) improves outcome in patients with heart failure (HF). However approximately 30% of patients are non-responsive to CRT. The purpose of this study was to investigate the role of the left ventricle (LV) mechanical dyssynchrony (MD) and scar burden assessment as predictors of CRT response. Methods: We included in the study 56 sinus rhythm patients (male 35 [62.5 %], mean age 57.0 ± 11.5 years) with ischemic or nonischemic HF, and left bundle branch block with QRS duration ≥ 150 ms who underwent CRT-D implantation. Echocardiography, full physical examination, myocardial perfusion imaging (MPI) with ^99mTc-methoxy-isobutyl-isonitrile and gated blood pool single-photon emission computed tomography (gBPS) were performed at baseline and at 6-month follow-up. Patients were grouped based on the response to CRT assessed by echocardiography. Results: Forty-five patients (80.3 %) were responder (RESP) and 11 (19.7 %) were non-responder (non-RESP) to CRT. RESP patients had higher LV anterior wall standard deviation (LV AW_SD) (p=0.0001) and lower summed rest score (SRS) (p=0.018) than non-RESP subjects. In multivariate logistic regression, LV AW_SD (adjusted odds ratio [OR] 1.5275; 95% confidence interval [CI] 1.1472-2.0340; p=0.0037), SRS (OR 0.7299; 95% CI 0.5627-0.9469; p=0.0178) and HF non-ischemic etiology (OR 20.1425; 95% CI 1.2719-318.9961; p=0.0331) were independent predictors of CRT response. Conclusion: Ventricle dyssynchrony and scar burden assessed by cardiac gBPS and MPI are associated with response to CRT. Further investigations of their predictive significance are warranted.