Subjective cognitive side effects (CSEs) are common in patients taking antiepileptic drugs (AEDs). The objective of this study was to predict which patients are at risk for CSEs, and compare the CSE profiles of all commonly used AEDs. In this nonrandomized retrospective study, medical records of 1694 adult outpatients with epilepsy seen at our center over a 5-year period who had taken one or more AEDs were examined. Non-AED predictors of CSEs were investigated, and rates of AED-related CSEs were compared in 1189 patients (546 on monotherapy) newly started on an AED at our center. The average rate of AED-related intolerable CSEs (leading to dosage change or discontinuation) was 12.8%. On multivariate analysis, no significant non-AED predictors of CSEs were found. Significantly more intolerable CSEs were attributed to topiramate (21.5% of 130 patients) than to most other AEDs, including carbamazepine (9.9%), gabapentin (7.3%), levetiracetam (10.4%), lamotrigine (8.9%), oxcarbazepine (11.6%), and valproate (8.3%). CSE rates with zonisamide (14.9%) were significantly higher than those for gabapentin and lamotrigine. After exclusion of CSEs during the first 8 weeks of therapy, rates of CSEs were lower, but relative differences remained unchanged. In monotherapy, significantly more intolerable CSEs occurred with topiramate (11.1% of 18 patients) than with carbamazepine or valproate, and both phenytoin and zonisamide were associated with more CSEs than valproate. From this study, it can be concluded that intolerable patient-reported CSEs are most common with topiramate, followed by zonisamide, phenytoin, and oxcarbazepine. They are least likely to be reported with gabapentin, valproate, lamotrigine, carbamazepine, and levetiracetam.