Background:  Cardiac resynchronization therapy (CRT) provides an excellent therapeutic option for patients with heart failure and reduced systolic functions, optimizing the CRT implantation procedure is mandatory to improve clinical response. The site of right ventricle (RV) pacing remains a puzzling issue that needs to be solved to assess the impact of non-apical RV pacing on CRT clinical and echocardiographic response. Objective:  To compare the impact of RV apical pacing versus RV septal pacing in patients with non-ischemic cardiomyopathy treated by CRT in terms of global longitudinal stain, 6 minutes walk test, and QRS complex width. Patients and Methods: An observational prospective trial study was conducted on 100 patients with dilated cardiomyopathy who were candidates for CRT implantation. Fifty consecutive patients had RV pacing lead in the apical position and the other 50 consecutive patients had the pacing lead in mid septal position. Results: The GLS significantly increased post-procedure within the whole patients (11.9 ±2 vs. 11 ±2.1), the apical group (12.1 ±1.9 vs. 11.1 ±2.1), and the septal group (11.8 ±2.1 vs. 10.9 ±2.1) (P < 0.001 for each). No significant difference was detected between both groups of patients regarding QRS width, 6 min walking test, and GLS. A positive correlation was found between delta GLS and % of 6 minutes walk test among the group of patients with mid-septal RV lead position. Conclusion: This study concluded that septal RV pacing is not superior to standard RV apical pacing in patients with non-ischemic cardiomyopathy candidate for CRT, in terms of clinical and echocardiographic response