Introduction/Aims Safety and outcomes data on eculizumab for generalized myasthenia gravis (gMG) in clinical practice remain limited. Outcomes and concomitant medication use may differ in practice compared with clinical trials. We analyzed the clinical and safety outcomes of patients who received eculizumab at our institutions. Methods Patients with acetylcholine receptor antibody positive (AChR+) gMG, who received ≥1 dose of eculizumab and had ≥1 follow‐up before December 10, 2021, were identified. Data were ed by chart review. Outcomes included MG Foundation of America Post Intervention Status (MGFA‐PIS), Clinical Classification (MGFA‐CC), MG‐Activities of Daily Living (MG‐ADL), concurrent immunomodulatory therapy use, and adverse events. Results Twelve patients were included. Mean age at eculizumab initiation was 57.4 y (range, 21–77). Eight had refractory MG. Four had history of thymoma and thymectomy. A mean of 3.2 (range, 2–5) immunomodulatory therapies were previously tried. Mean follow‐up duration was 18 mo (range, 2–21.6). Clinical improvement occurred rapidly; MGFA‐PIS was improved in 80%, and MGFA‐CC improved in 83% at 1 mo. Mean MG‐ADL decreased from 8.7 to 2.8 at 1 mo, and remained ≤3.5 over 1.5 y. Mean daily prednisone dose decreased from 22.5 mg to 7.2 mg at 1.5 y. Five of 7 patients discontinued maintenance IVIG or PLEX. No patients had meningococcal infections and adverse events were mild. Discussion Clinical improvement occurred in most patients after eculizumab initiation, beginning as quickly as 1 mo. Steroids were tapered and maintenance IVIG and PLEX were discontinued in most. Eculizumab had a favorable safety profile even when combined with other immunosuppressants.