Objectives Calcineurin inhibitors (CNI) are approved for the treatment of myasthenia gravis (MG) in Japan. However, the extent to which CNI have been effective remains unclear. Here we report data regarding CNI use and outcomes of MG. Methods We evaluated 640 consecutive MG patients by a multicenter survey. Patients not receiving any immune treatment were excluded, and cross-sectional and retrospective data of 515 patients receiving immune treatment with (n = 312) or without (n = 203) CNI were analyzed. Results Compared with patients treated without CNI, those treated with CNI had a higher frequency of MG Foundation of America Class III-V and higher severity disease at the worst clinical condition, and also had current higher severity, worse quality of life and higher daily doses of prednisolone, despite taking equivalent prednisolone dosages during the course of treatment. Achieving a treatment target was less frequent in the group treated with CNI. Onset age was not different between the two groups. Duration before CNI use after starting corticosteroids was 4.4 AE 6.3 years. Among those treated with CNI, late-onset MG patients achieved a more favorable current condition than did those with early-onset and thymoma-associated MG, whereas there was no such difference without CNI treatment. Conclusions CNI were given to severely ill MG patients with no attempt to select those more likely to respond, and failed to exert a strong impact on MG therapy. CNI should be given aggressively to patients with factors known to enhance susceptibility to these drugs, such as higher age at onset and early-stage disease.