OBJECTIVES:  Research examining epilepsy treatment satisfaction is lacking. The aim of this study is to compare treatment satisfaction among patients with epilepsy treated either with monotherapy or adjunctive therapy. METHODS:  Data from the 2011-2013 U.S. National Health and Wellness Survey (NHWS) were analyzed. The NHWS is a self-administered, internet-based survey of a nationwide sample of adults stratified to represent the demographic composition of the U.S. population. Patients who reported being treated with an antiepileptic drug (AED) for epilepsy were grouped as using monotherapy (one Rx) or adjunctive AED therapy (two or more Rxs). Patients provided information on treatment satisfaction with current epilepsy prescription medication (1 [extremely dissatisfied] to 7 [extremely satisfied]), demographics, and health characteristics (e.g., age, comorbidities [Charlson comorbidity index], epilepsy severity). Pairwise comparisons (Bonferroni adjusted) examined whether patients on monotherapy vs. adjunctive therapy differed in treatment satisfaction.  RESULTS:  Among 1,126 epilepsy patients (mean age=46.33; 47.70% female), 744 were on monotherapy (66.07%), 286 on two AEDs (25.40%), 65 on three AEDs (5.77%), and 31 on four or more AEDs (2.75%). Compared to monotherapy patients, treatment of patients with an increasing number of concomitant AEDs was associated with greater comorbidity burden (4+Rxs: 3.00 vs. monotherapy: 0.93), higher percentage of severe epilepsy (4+Rxs: 41.90% vs. monotherapy: 10.60%), and higher seizure frequency (4+Rxs: 35.50% vs. monotherapy: 7.30% for frequency > 1/week), all p<.05. Patients on monotherapy (5.93) had higher treatment satisfaction than patients on adjunctive therapy (4+Rxs: 4.78), p<.05. Additionally, among adjunctive therapy patients, those on 2Rxs (5.79) had higher satisfaction than those on 4+Rxs (4.78), p<.05. CONCLUSIONS:  In this study, monotherapy patients were more satisfied with their epilepsy treatment than adjunctive therapy users. The lower satisfaction levels among adjunctively-treated patients may be associated with the number of concomitant AEDs, seizure severity or frequency, comorbid conditions, or a combination of these factors.