This study examined the relationship between the APOE epsilon4 allele and postictal confusion in patients with medically intractable temporal lobe epilepsy (TLE). Patients with at least one epsilon4 allele (n=22) were three times more likely to exhibit postictal confusion (68%) than the 63 patients without epsilon4 (43%). These preliminary results demonstrate that APOE epsilon4 is associated with an increased risk of postictal confusion in patients with medically intractable TLE, suggesting possible dysfunction in neuronal recovery mechanisms.