Background: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction (HfrEF). Etiology may influence the outcome of patients undergoing CRT. Objective: to evaluate whether etiology (ischemic vs non-ischemic) influences the response to CRT and overall outcome. Methods: Our study included HFrEF patients undergoing CRT between January 2017-November 2019. We assessed right ventricle (RV) and left ventricle (LV) function using transthoracic echocardiography at baseline and one year after CRT. The response to CRT was defined by a decrease of more than 15% of left ventricle systolic volume. Patients were divided in two groups: ischemic and non-ischemic based on personal history. Adverse events (HF related hospitalizations and deaths) were tracked for 33± 12.8 months. Results: 52 patients undergoing CRT were included (64±13.5 years, 55.7% male, 70% non-ischemic etiology) The two groups were similar considering LV systolic baseline parameters and volumes. Ischemic etiology was associated with non-LBBB morphology on ECG (p=0.03), a more severe LV diastolic dysfunction using E/e ratio (p<0.05), and a more severe RV dysfunction using TAPSE (p=0.008) and RV fractional area change (FAC) (p<0.05). There was no significant difference in CRT response between ischemic and non-ischemic etiology. 14 (26.9%) patients had events (10 hospitalizations and 4 deaths) with a higher prevalence in the ischemic group (58.33% vs 25%, p=0.01). Univariate Cox regression analysis reported a higher risk of cardiovascular events for ischemic etiology (HR 2.4, 95% CI [0.8-8.1], p <0.05). In our cohort there was no significant difference in use of an implantable cardioverter-defibrillator in addition to CRT between ischemic and non-ischemic group (64.2% respectively 63.3%, p =0.3). Conclusion: Our study shows that ischemic and non-ischemic HF patients had similar response to CRT. However, ischemic etiology was associated with a higher risk of adverse cardiovascular events and a worse RV systolic dysfunction at baseline.