BACKGROUND: Regional Restitution Instability Index (R2I2) and Peak ECG Restitution Slope (PERS) are promising sudden cardiac death (SCD) risk markers. R2I2 and PERS use the standard 12鈥憀ead ECG to measure properties of electrical restitution implicated in ventricular arrhythmogenesis. We investigated the relationship between R2I2, PERS and autonomic function to inform future application of these risk markers. METHODS: Blinded, prospective, observational study of 44 patients with ischaemic cardiomyopathy undergoing risk stratification for an ICD. Patients underwent an electrophysiological study for determination of R2I2 and PERS. 24-hour ambulatory ECG monitoring was carried out for determination of time-domain heart rate variability (HRV). RESULTS: During median follow up of 22鈥痬onths, 11 patients experienced ventricular arrhythmia (VA)/SCD. Weak inverse correlation was seen between R2I2 and HRV-i (rho: -0.36, p鈥?鈥?.02). R2I2 and PERS were significantly higher in patients experiencing VA/SCD than those not (mean鈥?/-鈥疭EM:1.14鈥?/-鈥?.11 vs 0.84鈥?/-鈥?.05, p鈥?鈥?.01) and (1.73鈥?/-鈥?.27 vs 1.07鈥?/-鈥?.08, p鈥?鈥?.002) respectively. Patients with low HRV-i and high PERS had an incidence rate ratio for VA/SCD 14.5 times that of patients with high HRV-i and low PERS (p鈥?鈥?.02). CONCLUSION: This small study suggests that there is minimal correlation between R2I2, PERS and autonomic function as measured by HRV. Combining PERS with HRV identified patients at particularly high risk of ventricular arrhythmia/SCD. A combined PERS+HRV risk marker may improve SCD risk stratification in patients with ischaemic cardiomyopathy.