Vitamin D sufficiency has been associated with lower risk of multiple sclerosis and may also have a favorable effect on the course of the disease. The aim of this work was to identify predictors of serum 25-hydroxy vitamin D (25[OH]D) levels in persons with multiple sclerosis (MS) and to assess the effect of high-dose vitamin D(3) supplementation on vitamin D status. A 96-week randomized controlled trial was performed to assess the effect of supplementation with 20,000 IU of vitamin D(3) weekly on bone mineral density in 68 patients. We collected data on vitamin D intake and UV-exposure and repeatedly measured serum 25(OH)D levels. Half of the participants had sufficient winter vitamin D levels at baseline (≥ 50 nmol/l). Vitamin D status was predicted by sun exposure during the last 3 months and by ingested vitamin D from diet and supplements. In the placebo group, the proportion of the participants with sufficient levels increased from 55 % in winter to 92 % during the summer. In the intervention group, all participants had winter 25(OH)D levels above 50 nmol/l at the end of the study. MS patients who have no sun exposure and low dietary vitamin D intake during the winter months should be recommended to take vitamin D supplements to achieve serum 25(OH)D levels of at least 50 nmol/l.