Patients with epilepsy are at high risk for major depressive disorder (MDD) and, according to one report, postpartum depression (PPD) as well. The study described here sought to determine the prevalence and risk factors for PPD among women with epilepsy. Fifty-six women with epilepsy participating in a prospective study of perinatal antiepileptic drug (AED) pharmacokinetics were included. Participants completed the Beck Depression Inventory (BDI) during pregnancy and the postpartum period. Fourteen participants (25.0%) had a postnatal BDI score ≥12 indicative of PPD. Logistic regression indicated that significant risk factors for PPD among women with epilepsy included multiparity (odds ratio = 12.5) and AED polytherapy (odds ratio = 9.3). The rate of PPD was unaffected by the use of specific AEDs. In conclusion, PPD rates are higher among women with epilepsy than the general population, particularly those who are multiparous or receiving AED polytherapy, and there is no evidence that AED selection modifies this risk.