OBJECTIVES:  To compare health outcomes and associated costs among non-adherent patients with epilepsy using different classes of AEDs. METHODS:  Data from the 2014-2015 US National Health and Wellness Survey, a nationally representative, self-administered, internet-based survey, were analyzed. Non-adherence was assessed by the 8-item Morisky Medication Adherence Scale (non-adherence indicated by scores>0, with 0=perfect adherence). Patients were grouped by AED class: sodium channel blocker (SCB), gamma-aminobutyric acid analog (GABA), synaptic vesicle protein 2A (SV2A), or multiple mechanism (MM). Demographic and health characteristics evaluated included age, gender, and seizure severity. Outcomes evaluated included seizure frequency, health-related quality of life (HRQoL, short-form-36 (SF-36) version 2), work productivity and activity impairment (6-item WPAI), health resource utilization (HRU), and estimated mean annual direct and indirect costs. Adjusting for patient characteristics, generalized linear models were used to compare differences in outcomes by AED group. RESULTS:  Of 709 eligible patients, 236 (33%) were adherent and 473 (67%) were non-adherent. Adherence did not differ by AED class. Among non-adherent patients (mean age=42; 53% female), 245 (52%) received a SCB, 25 (5%) GABA, 99 (21%) SV2A, and 104 (22%) MM. After adjusting for covariates, GABA patients had more seizures in the past 30 days vs MM, SCB, or SV2A, (19.5 vs. 2.17, 2.62, 0.53; each p<0.001). Patients on SCB or SV2A vs. MM had higher mental component HRQoL scores (45.89, 45.57 vs. 40.02, both p<0.05), higher health utilities (0.69, 0.68 vs. 0.63, both p<0.05), less overall work impairment (11.80%, 7.09% vs. 60.68%, both p<0.05), and lower total indirect costs ($1,256, $345 vs. $20,783, both p<0.05). No differences in HRU and direct costs were observed. CONCLUSIONS:  In this nationally-representative survey, non-adherent patients with epilepsy treated with SCB and SV2A AEDs had fewer seizures, higher mental well-being and health utilities, decreased work impairment, and lower indirect costs versus other AED classes.