Real life data comparing the long-term outcome in patients with different heart diseases carrying an Implantable Cardioverter Defibrillator (ICD) are scarce. To compare the long-term risk of first appropriate ICD intervention and overall survival in patients with ICD and heart disease of different etiologies. Patients with an ICD implanted between January 1st, 2010 and December 31st 2022 followed in our Center were included. Study outcomes were all-cause mortality and first appropriate ICD intervention. A comparison between ischemic heart disease (IHD) and nonischemic heart disease (NIHD) was performed. In NIHD different etiologies of dilated cardiomyopathy (DCM) were analyzed. 1184 patients (592 IDH - 592 NIHD) were included. During a median follow-up of 53 months all-cause death occurred in 399 (34%) patients while first-appropriate ICD intervention occurred in 320 (27%). All-cause mortality was significantly higher in IHD vs NIHD patients (60% vs 43%; p<0.0001) but no differences in appropriate ICD intervention rate at 10-years (34% vs 40%; p=0.125) were observed. Among NIHD higher 10-year mortality rate were found in valvular heart disease, rctDCM and hypertensive DCM. Hypertrophic cardiomyopathy, alcoholic DCM (alcDCM) and post-radio/chemotherapy DCM (rctDCM) were the least arrhythmic phenotypes among NIHD. Of note, inappropriate interventions in alcDCM and rctDCM were higher than appropriate ones. Rate of ICD appropriate interventions and mortality is different according to the etiology of heart disease and cardiovascular risk profile; this should be taken into consideration in the prognostic stratification of these patients at the time of implantation.