The aim of this study was to assess factors that might influence the health-related quality of life (HRQoL) in patients with myasthenia gravis (MG). A cross-sectional study was performed including 230 consecutive patients with MG. Severity of the disease was estimated according to the MGFA classification and QMG score. HRQoL was assessed by the SF-36 questionnaire. Depressive and anxiety symptoms were assessed using the Hamilton rating scales for depression and anxiety, respectively. Social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS), and acceptance of the disease by the Acceptance of Illness Scale. The significant demographic predictors of worse HRQoL in MG patients were older age (p = 0.025) and lower education (p = 0.012). Among clinical features, significant independent contributing factors of worse HRQoL were more severe form of the disease according to MGFA (p = 0.001) and higher QMG score (p = 0.001). Finally, psychosocial predictors of worse quality of life were lower MSPSS score (p = 0.001), poor acceptance of the disease (p = 0.001), as well as higher levels of anxiety and depression (p = 0.001). Our study revealed that the HRQoL in patients with MG is similarly reduced in its psychological and physical aspects. These results may have a practical implication pointing out that different aspects of psychosocial support should be added to the regular therapeutic protocols.