OBJECTIVE: To test the hypothesis that individual antiepileptic drugs (AEDs) are not associated with cognitive impairment beyond other clinically relevant factors, we performed a cross-sectional study of patients admitted to an inpatient video-EEG monitoring unit. METHODS: We prospectively enrolled patients admitted to an inpatient specialist epilepsy program between 2009 and 2016. Assessments included objective cognitive function, quality of life subscales for subjective cognitive function, and questionnaires for anxiety and depressive symptoms. Bayesian model averaging identified predictors of cognitive function. Bayesian model selection approach investigated effect of individual AEDs on cognition. Conventional frequentist analyses were also performed. RESULTS: A total of 331 patients met inclusion criteria. Mean age was 39.3 years and 61.9% of patients were women. A total of 45.0% of patients were prescribed AED polypharmacy, 25.1% AED monotherapy, and 29.9% no AED. Age, seizure frequency, and a diagnosis of concomitant epilepsy and psychogenic nonepileptic seizure were predictors of objective cognitive function. Depression, anxiety, and seizure frequency were predictors of subjective cognitive function. Individual AEDs were not independently associated with impaired cognitive function beyond other clinically relevant variables. CONCLUSIONS: This study found that no AED was independently associated with cognitive dysfunction. Significant determinants of objective and subjective cognitive dysfunction included seizure frequency and depression, respectively. These findings suggest that optimizing therapy to prevent seizures is not likely to occur at the expense of cognitive function.