Short-term randomized trials showed that Betaseron reduces relapses, new MRI lesions, and disability progression in Multiple Sclerosis. However, has it been effective for over 15 years? This extension study of the BENEFIT trial in clinically isolated syndrome (people with a first attack of demyelinating disease) seeks to answer that question. We review the effects on relapses, MRI lesions, disability, cognitive performance, employment, and quality of life.