Objectives Emerging evidence suggests that fatigue in myasthenia gravis (MG) is a relevant problem that negatively impacts activities of daily living (ADL). Prevalence of fatigue was assessed using the Chalder Fatigue Scale (CFQ). Impact of fatigue on ADL and QoL was assessed by the MG activities of daily living profile (MG‐ADL) and the MG‐specific quality‐of‐life instrument (MG‐QoL) respectively. Association of fatigue with sociodemographics clinical characteristics of MG and comorbidities including mood and anxiety disorders as well as sleep disorders was investigated using multivariable logistic PRL regression analyses. Results Overall 200 MG patients were included. The observed rate of fatigue was 56.1% of those 70.4% fulfilled the criteria of chronic fatigue (CF) with a duration of ≥6?months. Relevant fatigue was strongly associated to ADL and QoL. Factors associated with relevant fatigue were disease severity and depressive state. Furthermore positive muscle‐specific tyrosine kinase (MuSK) antibody status showed a strong association with relevant fatigue. Conclusions MG patients have a high prevalence of fatigue which negatively impacts ADL and QoL. MG‐specific clinical characteristics are related to fatigue and might help to identify MG patients at risk for fatigue. Keywords: Astragaloside III activities of daily living cohort studies depression fatigue myasthenia gravis quality of life 1 Fluctuating painless muscle weakness is usually referred to as cardinal symptom of myasthenia gravis (MG; Cejvanovic & Vissing 2014 Grob Brunner Astragaloside III Namba & Pagala 2008 However the clinical picture of MG is more complex and emerging evidence recognizes fatigue as a relevant problem in MG (Elsais Wyller Loge & Kerty 2013 Paul Cohen Goldstein & Gilchrist 2000 Previous studies reported fatigue prevalence rates between 75% and 89% in MG patients (Kluger Krupp & Enoka 2013 and qualitative data suggest that in some patients fatigue has a greater impact on daily living of MG patients than has muscle weakness (Barnett Bril Kapral Kulkarni & Davis 2014 Zwarts Bleijenberg & van Engelen 2008 However overall literature on fatigue in MG is scarce and its impact on activities of daily living (ADL) and quality of life (QoL) has never been systematically explored. This might be due to various reasons. Fatigue is a complex nonspecific and highly subjective symptom and therefore difficult to evaluate and quantify (Krupp LaRocca Muir‐Nash & Steinberg 1989 Norheim Jonsson & Omdal 2011 The fluctuating and effort‐dependent nature of fatigue makes it even more difficult to separate fatigue from muscle fatigability in MG. We follow recent proposals to use the term fatigue to refer to subjective sensations of exhaustion and muscle fatigability to refer to objective changes in muscle performance (Kluger Astragaloside III et?al. 2013 Other related phenomena such as depression and sleep disorders need to be distinguished from fatigue and should therefore be included as covariates when assessing fatigue (Kluger et?al. 2013 Finally the understanding of the pathophysiology of fatigue is limited. MG is an autoimmune‐mediated disease with autoantibodies directed against components of the postsynaptic muscular endplate (Szczudlik et?al. 2014 The most likely confinement to the peripheral nervous system makes hypotheses on the pathophysiology of fatigue in MG particularly challenging. The aim of the present study was to assess the prevalence of fatigue and its impact on ADL and QoL in a large cohort of MG patients as well as to identify factors associated with fatigue including MG‐specific clinical characteristics as well as potential confounders such as mood and sleep disturbances (Elsais et?al. 2013 Kluger et?al. 2013 2 and Methods 2.1 Patients This was a cross‐sectional observational study performed at the certified Astragaloside III Integrated Center for Myasthenia gravis (IMZ) of the Charité – Universit?tsmedizin Berlin Germany. Patients over the age of 18?years with confirmed diagnosis of myasthenia gravis were included independent of disease duration and severity (excluding myasthenic crisis). Patients were consecutively screened at the IMZ clinic between December 2012 and December 2013. Sociodemographics (age sex) current MG‐specific medication (cholinesterase inhibitors.