We previously showed that oral cholecalciferol and ergocalciferol have comparable effects in decreasing circulating parathyroid hormone (PTH), despite a greater increase in total serum 25-hydroxyvitamin D (25OHD) concentration with cholecalciferol supplementation. However, the effects of cholecalciferol and ergocalciferol on total serum 1,25-dihydroxyvitamin D (1,25(OH)D), vitamin D-binding protein (DBP), free 25OHD and free 1,25(OH)D concentrations have not been previously studied.We randomized 95 hip fracture patients (aged 83±8years) with vitamin D deficiency (serum 25OHD 0.05, post-treatment vs baseline). Both treatments were associated with comparable increases in DBP (cholecalciferol: +18%, ergocalciferol: +16%, p=0.32 between groups), albumin (cholecalciferol: +31%, ergocalciferol: +21%, p=0.29 between groups) and calculated free 25OHD (cholecalciferol: +46%, ergocalciferol: +36%, p=0.08), with comparable decreases in free 1,25(OH)D (cholecalciferol: -17%, ergocalciferol: -19%, p=0.32 between groups). In the treatment-adherent subgroup the increase in ionized calcium was marginally greater with cholecalciferol compared with ergocalciferol (cholecalciferol: +8%, ergocalciferol: +5%, p=0.03 between groups). There were no significant differences between the treatments in their effects on the calculated bioavailable concentrations or free indices of the vitamin D metabolites (p>0.05 between groups).In vitamin D-deficient hip fracture patients, oral supplementation with cholecalciferol and ergocalciferol had no effect on total serum 1,25(OH)D, and comparable effects on DBP and free vitamin D metabolite concentrations. This is despite cholecalciferol having greater effects than ergocalciferol in increasing total 25OHD, and in increasing ionized calcium in treatment-adherent subjects. These findings may explain why cholecalciferol and ergocalciferol supplementation result in similar magnitudes of PTH reduction, but implicate potential differences in other vitamin D metabolites, such as 24,25(OH)D, that could explain their different effects on ionized calcium.