BACKGROUND: Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic intervention for multiple sclerosis (MS) that has gained increased attention in the last decade. The impact of this intervention on the quality of life (QoL) of patients with MS remains unclear. OBJECTIVE: The aim of this study was to investigate the impact of AHSCT on QoL in patients with MS using Multiple Sclerosis Impact Scale (MSIS-29) scores. METHODS: In this observational retrospective cohort study, patients with relapsing-remitting MS treated with AHSCT in Sweden from 2004, when the first transplant was performed, until 31 December 2019, were considered for participation. Anonymized outcome data were extracted from the Swedish MS registry in May 2022. RESULTS: Out of 213 patients assessed for eligibility in the study, 96 were included in the final analysis. After a median follow-up of 5.2 (IQR 3.2-6.8) years, 58% improved, 14% remained unchanged and 28% worsened in the physical domain of the MSIS-29. In the psychological domain, 63% improved, 18% remained unchanged and 19% worsened. Improvements in both domains occurred early, within the first year following intervention. CONCLUSIONS: Treatment intervention with AHSCT is associated with a clinically meaningful improvement in QoL.