Objective:to examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting.Methods:retrospective cohort study on PwMS treated with AHSCT at two centers in London, UK, consecutively between 2012 and 2019 who had ≥ 6 months of follow-up or died at any time. Primary outcomes were survival free of MS relapses, MRI new lesions and worsening of expanded disability status scale (EDSS). Adverse events rates were also examined.Results:the cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS (RRMS). At baseline, the median expanded disability status scale (EDSS) was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6–85). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of subjects at 2 years and 85% at 4 years. EDSS progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. EBV reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplant-related deaths within 100 days (2.5%), all following fluid overload and cardiac or respiratory failure.Conclusions:efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher.Classification of evidence:this study is rated Class IV because of the uncontrolled, open-label design.