OBJECTIVE: To study the diagnostic value of volume perfusion CT (VPCT) in patients with transient focal neurological deficits following and during epileptic seizures, that mimic symptoms of stroke. METHODS: a retrospective case-control study was performed on 159 patients that presented with a seizure and received an emergency VPCT within the first 3.5 hours of admission, after being misjudged to have an acute stroke. The reference test was a clinical-based, EEG-supported diagnostic algorithm for seizure. RESULTS: We included 133 patients: 94 stroke-mimicking cases with postictal focal neurological deficits (“Todd’s phenomenon”, n=67) or ongoing seizure on hospital admission (“ictal patients”, n=27), and 39 postictal controls without focal neurological deficits. Patients with Todd’s phenomenon showed normal (64%), hypo (21%)- and hyperperfusion (14%) on early VPCT. Ictal patients displayed more hyperperfusion compared to postictal patients (p=0.015). Test sensitivity of hyperperfusion for ictal patients is 38% CI [20.7-57.7], specificity 86% CI [77.3-91.7], positive predictive value (ppv) is 42% CI [27.5-58.7], the negative predictive value (npv) 83% CI [78.6-86.9]. A cortical distribution was seen in all hyperperfusion scans, compared to a cortico-subcortical pattern in hypoperfusion (p<0.001). A history of complex focal seizure and age were associated with hyperperfusion (p= 0.046 and 0.038, respectively). CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that VPCT accurately differentiates ictal stroke mimics from acute ischemic stroke. CONCLUSION: VPCT can differentiate ictal stroke mimics with hyperperfusion from acute ischemic stroke, but not postictal patients who display perfusion patterns overlapping with ischemic stroke.