Objective To evaluate the long-term costs and quality of life (QoL) with and without disease-modifying treatments (DMTs) of patients with multiple sclerosis (MS). Methods Data on resource consumption, productivity losses, QoL (utility), and fatigue were collected from 1355 patients registered with a patient association and descriptive analyses was performed. A Markov model was developed to estimate costs and utility over 20 years using the survey data. Disease progression without DMTs was taken from an epidemiological cohort in France (EDMUS cohort, LYON). Progression under DMTs was estimated from the Stockholm MS registry. Results are presented as cost per quality-adjusted life-years (QALYs), from the societal perspective, in (sic)2007, discounted at 3%. Results Mean Expanded Disability Status Scale (EDSS) was 4.4 and mean total annual costs per patient were (sic)44,400, of which 47% were productivity losses and 11% informal care. Public payers cover an estimated 48% of costs. Mean utility was 0.52, and the loss compared with the normal population was estimated at 0.28. Costs and utility ranged from (sic)16,000 and 0.79 at EDSS 1 to (sic)76,000 and 0.11 at EDSS 8-9. Over 20 years, costs were estimated at (sic)429,000 and QALYs at 8.96 for patients without DMTs and at (sic)433,207 and 9.24 QALYs if all patients were starting treated with DMTs at EDSS 1-3. Conclusion Although the data for this analysis come from different sources, the results indicate that the cost increase with DMTs is moderate. Multiple Sclerosis 2009; 15: 741-751. http://msj.sagepub.com