Veterans and patients with epilepsy are at higher risk of suicide than the general population. Some studies suggest that antiepileptic drugs (AEDs) further increase the risk of suicide. The nature of the relationship between suicidality and epilepsy treatment needs clarification. We examined this relationship in a cohort of veterans with seizures.We performed a retrospective chart analysis of patients at the Philadelphia VA Medical Center with a diagnosis of seizure disorder between January 2000 and April 2007. Patients with suicidal ideation and/or suicidal behaviors were analyzed with respect to the following risk factors: age, history of traumatic brain injury (TBI), substance abuse and AED prescription.526 charts were reviewed, 385 of which met inclusion criteria. Patients with substance abuse were more likely to have suicidal ideation (adjusted odds ratio 3.37, 95% CI 1.84 -6.18). Risk decreased with age (adjusted odds ratio 0.94, 95% CI 0.92 - 0.97 for each year). There was no statistically significant relationship between suicidality and AED use or history of TBI.In our population, AEDs were not associated with increased risk of suicidality, whereas substance abuse was associated with a substantial risk increase. The interactions among seizures, suicidality, substance abuse and other neuropsychiatric diseases are complex. Large-scale studies in patients with seizures are needed to understand the impact of individual drugs and other contributing factors. Providers should be cautious not to withhold potentially beneficial treatment, however patients with risk factors such as history of substance abuse should be followed closely after AED initiation or adjustment.