Cardiac resynchronization therapy (CRT) is a recently introduced therapeutic option for patients with severe heart failure and intraventricular conduction disturbances. However, it is estimated that 20% to 30% of patients may not respond to CRT. Patients with ischemic cardiomyopathy (IC) may respond less favorably to CRT compared with patients with idiopathic dilated cardiomyopathy (IDC). Accordingly, the beneficial effects of CRT were evaluated in 2 subsets of patients (IC and IDC). Seventy-four patients with end-stage heart failure, New York Heart Association (NYHA) class III or IV, left ventricular (LV) ejection fraction <35%, QRS >120ms, and left bundle branch block received a biventricular pacemaker. At baseline and 6 months after implantation these parameters were evaluated: NYHA class, Minnesota quality-of-life score, QRS duration, and 6-minute walking distance. LV ejection fraction and severity of mitral regurgitation were assessed before and 6 months after CRT using 2-dimensional echocardiography. Long-term follow-up and hospitalization rates were obtained up to 2 years. Of the 74 patients, 46% (n = 34) had IC and 54% (n = 40) IDC. At 6 months follow-up all clinical parameters, QRS duration, LV ejection fraction, and mitral regurgitation improved significantly in both groups. Long-term (2-year) follow-up showed a survival rate of 87.5% for patients with IDC and 88.3% for patients with IC. The percentages of responders to CRT (defined as an improvement in NYHA class >or=1 grade) were comparable in both groups (65% vs 71%). Therefore, the underlying etiology of heart failure (IC vs IDC) was not related to the response to CRT.