The necessity of implantable cardioverter-defibrillator (ICD) implantation in patients with systolic heart failure (HF) who undergo cardiac resynchronization therapy (CRT) may be questioned. The aim of this study was to identify patients at low risk for sustained ventricular arrhythmia. One hundred sixty-nine consecutive patients with HF (mean age 60 +/- 12 years, 125 men, 73% in New York Heart Association class III) referred for CRT and prophylactic, primary prevention ICD implantation underwent baseline clinical and echocardiographic assessment and regular device follow-up. The primary study end point was appropriate ICD therapy. During a mean follow-up period of 654 +/- 394 days, 35 patients (21%) had sustained ventricular arrhythmias requiring appropriate ICD therapy. Of the 3 patients who experienced sudden cardiac death, 2 had been treated with appropriate ICD therapy before sudden cardiac death. In a multivariate model, only history of nonsustained ventricular tachycardia (p = 0.001), a severely (<20%) decreased left ventricular ejection fraction (p = 0.001), and digitalis therapy (p = 0.08) independently predicted appropriate ICD therapy. Patients with 0 (n = 46), 1 (n = 36), 2 (n = 73), and 3 (n = 14) risk factors for appropriate ICD therapy had a 7%, 14%, 27%, and 64% and 0%, 6%, 10%, and 43% incidence of appropriate ICD therapy for ventricular arrhythmias and for rapid ventricular tachycardia or ventricular fibrillation, respectively. In conclusion, apart from commonsense considerations (age and significant co-morbidities), ICD addition seems ineffective in CRT patients without nonsustained ventricular tachycardia, digoxin therapy, and severely reduced left ventricular systolic function.