Introduction Cardiac resynchronization therapy combined with an implantable cardioverter defibrillator (CRT-D) is widely applied in heart failure patients. Sufficient data on arrhythmia and defibrillator therapies during long-term follow-up of more than 4 years are lacking and data on mortality are conflicting. We aimed to characterize the occurrence of ventricular arrhythmia, respective defibrillator therapies and mortality for several years following CRT-D implantation or upgrade. Material and methods Eighty-eight patients with ischemic (ICM) or non-ischemic dilated cardiomyopathy (DCM) and at least one CRT-D replacement were included in this study and analyzed for incidence of non-sustained ventricular tachycardia (NSVT), defibrillator shocks, anti-tachycardia pacing (ATP) and mortality. Results ICM was the underlying disease in 59%, DCM in 41% of patients. During a mean follow-up of 76.4 ±24.8 months the incidence of appropriate defibrillator therapies (shock or ATP) was 46.6% and was elevated in ICM compared to DCM patients (57.7% vs. 30.6%, respectively; p = 0.017). Kaplan-Meier analysis revealed significantly higher ICD therapy-free survival rates in DCM patients ( p = 0.031). Left ventricular ejection fraction, NSVT per year and ICM (vs. DCM) were independent predictors of device intervention. The ICM patients showed increased mortality compared to DCM patients, with cumulative all-cause mortality at 9 years of follow-up of 45.4% and 10.6%, respectively. Chronic renal failure, peripheral artery disease and chronic obstructive pulmonary disease were independent predictors of mortality. Conclusions The clinical course of patients with ICM and DCM treated with CRT-D differs significantly during long-term follow-up, with increased mortality and incidence of ICD therapies in ICM patients.