BACKGROUND AND PURPOSE: The insula of the right cerebral hemisphere may have a major role in cardiac autonomic control. This study was aimed at assessing the effects of acute right insular ischemic damage on heart rate variability (HRV) and arrhythmias. METHODS: Holter monitoring for 24 hours was performed in 103 consecutive patients with first-ever acute ischemic stroke. Time and frequency domain measures of HRV and arrhythmias were considered in all cases. RESULTS: Forty-nine patients (47.5%) had a right-sided infarction, whereas 54 (52.5%) had a left-sided infarction. Insular involvement was present in 33 patients with right-sided stroke (67.3%) and in 36 patients with left-sided stroke (66.6%). When compared with all other stroke patients, subjects with right-sided insular damage showed significantly lower values of the standard deviation of all normal-to-normal (SDNN) R wave to R wave (RR) intervals and of the root mean square of differences (rMSSD) of adjacent normal-to-normal RR intervals, and higher low-frequency/high-frequency ratio values (P<0.05). Right insular stroke was also associated with more complex arrhythmias than any other localization (P<0.05). Moreover, in the whole population of stroke patients, lower values of SDNN were associated with the presence of more frequent and complex arrhythmias. CONCLUSIONS: These findings further support the notion that the right insula is implicated in the autonomic control of cardiac activity and that acute right insular damage may lead to a derangement of cardiac function with potential prognostic implications.