Modest and even severe vitamin D deficiency has become a worldwide health issue and the diagnosis of a condition of vitamin D deficit is followed by the supplementation of food enriched with vitaminD or of vitamin D supplements. Cholecalciferol and ergocalciferol are the most widely used compounds. Calcifediol, the direct precursor of calcitriol (25OHD) biomarker of vitamin gas and the vitamin D status is rarely mentioned as first intervention. Supplementation with calcifediol has demonstrated efficacy in short- and long-term clinical trials, with stable and sustained 25OHD concentrations with no associated safety concerns. The most remarkable difference between cholecalciferol and calcifediol in terms of change in serum 25OHD3 levels is the faster and more potent effect by calcifediol. Oral calcifediol has also a higher rate of intestinal absorption versus cholecalciferol with important implications in conditions of decreased intestinal absorption. These evidences will be evaluated and discussed during my presentation.