Background and purpose: The recent report on Value-of-Treatment (VoT) project highlights the need for early diagnosis-intervention, integrated, seamless care underpinning timely care pathways and access to best treatments. The VoT-multiple-sclerosis (MS) economic case study analysis aimed to estimate the effectiveness/cost-effectiveness of both early treatment and reducing MS risk factors (e.g. smoking and vitamin D insufficiency). Methods: A series of decision analytical modellings were developed and applied to estimate the cost-effectiveness of: (1) reducing the conversion from clinically-isolated-syndrome (CIS) to clinically-definite-MS (CDMS); (2) smoking cessation and increase of 25 hydroxyvitamin D (25(OH)D) serum level. Both (1) and (2) considered socioeconomic impact on averted MS disability progression. Costs were reported for societal and healthcare provider perspectives (pending on data across nations; Euros). Effectiveness was expressed as Quality-Adjusted-Life-Years (QALYs) gains. Long term (25, 30, 40,50-years) and short (one-year) timelines were considered for (1) and (2), respectively. Results: Early treatment was cost-effective for the health care provider and both cost-effective/cost-saving for the society across time-horizons and nations. Smoking cessation and an increase of 25(OH)D in MS patients were both cost-effective/cost-saving across nations. Conclusions: To the best of our knowledge, our work provides the first economic evidence to base appropriate public health interventions to reduce the MS burden in Europe.