To assess the efficacy and safety of a single cholecalciferol loading protocol in nursing home (NH) residents taking no VitD supplementation at regular basis. Randomized single-blind controlled study. One NH. All residents. From March 21st to May 19th, 2015, NH residents were randomly assigned to either 4x100'000IU to be taken every 2 weeks (treatment group) or an individualized regimen according to baseline 25(OH)VitD level (control group). 25(OH) VitD, calcium, phosphorus, parathyroid hormone, alkaline phosphatase, and creatinine serum levels were centrally measured at day 7 after the last dose in both groups, and at baseline in the control group. 111 residents (mean age 85.1 +/- 6.7 years) were randomized to the treatment (N=53) or the control group (N=58). No significant difference in terms of demographic characteristics, risk for osteoporosis, and past history of VitD supplementation was measured. At baseline, 37.9%, 25.5% and 5.2% were respectively sub-optimal, insufficient, and deficient for VitD. Whatever the study group, at the 7th day after the last dose of cholecalciferol, 100% of residents reached serum values ae20ng/mL (p value for non-inferiority < 0.001 and p value for superiority p=1.00) and 93.6 vs. 88.2% reached values ae30ng/mL in the treatment and control group respectively (p value for non-inferiority < 0.01 and p value for superiority p=0.48). While mean value was higher in the treatment group (50.2 +/- 15.4 vs. 35.8 +/- 6.5ng/mL; p150 ng/mL. Not any biological adverse effects was measured. This study confirmed that a single loading protocol is at least as effective and safe as tailored regimen in terms of the ability to rapidly normalize 25(OH)VitD values. The often required dosage of 25(OH)VitD is reasonably not necessary to initiate VitD supplementation protocol in this vulnerable population.