Stroke is a well-known cause for seizures in the adult population. Research in animal models indicates that abnormalities in the blood-brain barrier (BBB) permeability can play a role in the development of spontaneous seizures or status epilepticus. The integrity of the BBB was investigated in patients with late post-stroke seizures by performing DTPA-SPECT studies to evaluate the correlation of BBB dysfunction in late post-stroke seizures. All patients with late-onset post-cortical stroke seizures hospitalized during 2009-2010 underwent a brain DTPA-SPECT within 72 h of the first seizure and were compared to a control group of stroke patients without seizures. Twenty-eight patients were included in the study. Twelve out of 14 (85.7%) in the group of seizure post-stroke patients had a positive brain DTPA-SPECT showing disruption of the BBB in the region of the stroke respective to four patients out of 14 (28.6%) in the control group of stroke patients without seizures (p = 0.001). The results of this study suggest that there is a correlation between late post-stroke seizures and BBB disruption, as revealed by DTPA-SPECT examination. Perhaps, this finding could lead to the hypothesis that the BBB disruption can predict developing seizures in patients with cortical stroke.