Objectives: We investigated the diagnostic accuracy of fragmented QRS (fQRS) numbers in surface electrocardiogram (ECG) in heart failure (HF) patients for prediction of cardiac resynchronization therapy (CRT) non-responders. Methodology: In this study, patients with HF who were candidates for CRT implantation were enrolled. A 12-lead surface electrocardiogram was conducted with the aim of finding fQRS. Presence of more than 2 notching in the R or S wave in wide QRS complexes in at least two adjacent leads corresponding to a coronary bed, considered as fQRS. All patients underwent transthoracic echocardiography 3-6 months after the CRT implantation for the evaluation of Left Ventricular End Diastolic Volume (LVEDV), Left Ventricular End Systolic Volume (LVESV), and Left ventricle ejection fraction (LVEF). The data were analyzed by SPSS v.22 software. P-value of less than 0.05 considered significant. Results: We investigated on a total of 73 patients with HF that 64.38% of them responded to CRT. Most of responders were patients without fQRS complexes (80%). LVEF, LVESV, and LVEDV were different significantly before and after CRT implantation in patients with fQRS (p<0.001). Our results showed that the presence of at least one fQRS can lead to non-responsiveness to CRT. Therefore, we take cut-off point equal-greater than one into account as the best cut-off point for response to CRT. The area under the curve (AUC) for CRT prediction was 0.715 (95% CI: 0.598-0.815, P=0.003). Conclusion: In conclusion, the presence of even one fQRS in the surface ECG can predict CRT non-responsiveness with good accuracy.