Efficacy of alemtuzumab retreatment (course [C] 3) after the initial 2 courses were evaluated (CARE-MS II, NCT00548405; extension, NCT00930553). Patients received alemtuzumab retreatment (12 mg/day, 3 consecutive days;≥12 months apart) as needed for relapse and/or MRI activity or another disease-modifying therapy (DMT) per investigator’s discretion. Assessments 12 months before C3 and up to 3 years after C3: annualised relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus core study baseline); 6 month confirmed disability improvement (CDI). Patients receiving another DMT were excluded. Analyses included patients who received C3 or more, with data censored at the time of C4 if a fourth course was received. Through Year 6, 88% of patients entering the extension remained on study, with 45% receiving ≥1 retreatment. ARR decreased from 0.85 (12 months before C3) to 0.20 (12 months after C3; rate ratio [95% CI], 0.24 [0.17–0.34]; p<0.0001), and remained low (0.27) 3 years after C3. 68% of patients maintained stable/improved EDSS 12 months after C3. The percentage with CDI increased from 4% (12 months before C3) to 14% (12 months after C3; p=0.0126). These findings demonstrate the efficacy of alemtuzumab C3 in patients with disease activity after the initial 2 courses.Study support: Sanofi and Bayer HealthCare Pharmaceuticals.