© 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Myasthenia gravis (MG) may be refractory to traditional therapies. Quality of life (QOL) and disease burden in patients with refractory and nonrefractory MG were compared using Myasthenia Gravis Foundation of America MG Patient Registry data.Methods:Adults aged 18 years or older with MG diagnosed ≥2 years before enrollment were included. Participants with refractory MG had received ≥2 previous and 1 current MG treatment and had MG Activities of Daily Living Scale total score ≥6 at enrollment; other participants had nonrefractory MG. MG QOL 15-item scale (MG-QOL15) scores were compared.Results:In total, 56 participants with refractory and 717 participants with nonrefractory MG enrolled. Participants with refractory MG had significantly higher mean (SD) MG-QOL15 total scores [31.4 (11.1) vs. 20.8 (15.0), P < 0.0001] and were more likely to have had exacerbations, emergency department visits, and recent hospitalizations.Conclusions:Participants with refractory MG experience worse QOL and greater clinical burden than those with nonrefractory disease.