OBJECTIVES: Delirium is an acute fluctuating disorder of attention and awareness. It is associated with autonomic dysfunction and increased mortality. The primary endpoint of our study was to measure autonomic activity in acute stroke patients, by means of heart rate variability analysis, in order to identify autonomic modifications that can predispose to delirium. METHODS: Patients were consecutively enrolled from the stroke unit. Inclusion criteria were age >/= 18 years and diagnosis of stroke with onset within the previous 72 h confirmed by neuroimaging. Exclusion criteria were atrial fibrillation, congestive heart failure, and conditions requiring intensive care unit. Patients were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at baseline, after 72 h, or when symptoms suggesting delirium occurred. For each patient, ECG was recorded at baseline assessment and HRV analysis was conducted on five consecutive minutes of artifact-free ECG traces. RESULTS: Fifty-six ECGs were available for analysis. During the study period, 11 patients developed delirium. Patients with and without delirium did not differ for sex, age, severity of stroke, and comorbidities. The delirium group had greater standard deviation of the heart rate (DLR - :9.16 +/- 8.28; DLR + : 14.36 +/- 5.55; p = 0.026) and lower power spectral density of the HF component (DLR - : 38.23 +/- 19.23 n.u.; DLR + : 25.75 +/- 8.77 n.u.; p = 0.031). CONCLUSIONS: Acute non-cardioembolic stroke patients with increased variability of heart rate and decreased vagal control are at risk for delirium.