OBJECTIVE: We aimed at evaluating the combined use of heart rate variability (HRV), baroreflex sensitivity (BRS), and MIBG imaging in the risk stratification for sudden cardiac death (SCD) of patients with mild to moderate heart failure. METHODS: Twenty-five patients (17 male and 8 female, mean age 63 +/- 5 years, mean LVEF 36 +/- 3%) with a recently implanted defibrillator (ICD) and mild (NYHA I-II) heart failure due to either ischemic (n = 15) or dilated (n = 10) cardiomyopathy were studied. One week after ICD implantation they underwent (a) baroreflex sensitivity (BRS) evaluation to bolus phenylephrine by the Oxford method, (b) 24-h heart rate variability (HRV) assessment, and (c) MIBG imaging. The mean patient follow-up was 32 +/- 10 months. Simple correlation and stepwise multiple regression analysis was performed to evaluate (a) if the number of sustained ventricular tachycardia (cycle length <330 ms) or fibrillation episodes per month is related to one or more of MIBG, BRS, and HRV indexes and (b) if MIBG % washout is related to HRV and/or BRS. RESULTS: The frequency of fast ventricular arrhythmic episodes (FVAE) demonstrated an inverse relation to BRS (p < 0.0001), rMSSD (p = 0.001), and pNN50 (p = 0.0034), while it was positively related to LF (p < 0.0001) and MIBG % washout (p = 0.001). BRS, LF, rMSSD, and MIBG washout were also independent predictors of FVAE. MIBG washout was related to only one HRV marker (SDNN-I, p < 0.0001), while no correlation was observed with BRS. CONCLUSIONS: In ICD recipients with well-compensated heart failure, autonomic markers derived from BRS, HRV, and MIBG studies are related to FVAE. These markers have limited inter-dependency and constitute useful means for SCD risk stratification in this subgroup of patients.