We aimed to assess the safety and efficacy of high-dose intermittent vitamin D supplementation in adolescents. Twenty-two healthy adolescents with serum 25 hydroxy-vitamin D (25-OHD) of 12.5-50 nmol/l were randomised to receive 300,000 IU or 150,000 IU of vitamin D3, or placebo orally 6-monthly for 1 year. At 12 months, the average vitamin D levels for the 300,000 IU, 150,000 IU and placebo groups were 63.0, 41.1 and 35.8 nmol/l, respectively, (P=0.004 for difference between 300 000 IU group and placebo after adjustment for age, sex and seasonal variation). At 12 months, one participant receiving 300,000 IU was mildly deficient (25-OHD 49 nmol/l), whereas five out of six (83%) in the placebo and four out of seven participants (57%) in the 150,000 IU group remained deficient. There were no adverse events. Compliance was high. This suggests that 300,000 IU vitamin D3 orally 6-monthly may safely and effectively correct vitamin D deficiency in adolescents.