BACKGROUND: Autonomic nervous system (ANS) malfunction is a common sequel of stroke. The impact of lesion configuration on the expression of stroke-related ANS malfunction is largely unknown. OBJECTIVE: To examine the relationship between stroke location and ANS malfunction, as reflected in cardiac rhythm control. METHODS: 25 patients in the subacute phase post first-ever ischemic stroke were recruited for the study. Heart rate monitor (RS800CX) was used to record RR intervals analyzed as heart rate variability (HRV) parameters. Lesion data derived from follow-up CT scans of the brain was used for voxel-based lesion symptom mapping (VLSM) analysis (MEDx software, Medical Numerics) to identify voxels of the normalized brain where damage exerts a significant impact on the HRV scores. RESULTS AND CONCLUSION: ANS control of the cardiac rhythm, as expressed in the HRV, was affected by damage to a large array of cortical and subcortical structures in the right hemisphere. In the left hemisphere only damage confined to a small set of subcortical structures was shown to exert a significant impact on the recorded HRV measures. In addition, VLSM analysis disclosed a different pattern of cerebral control over two widely used standard time-dependent measures of the HRV - SDNN and RMSSD, with the former being sensitive to damage in a much larger array of structures in both hemispheres.