The safety considerations of food-based solutions for vitamin D deficiency prevention, such as fortification and supplementation, are critical. On the basis of collective data from 20 randomized controlled trials (RCTs) and 20 national healthy surveys, as well as prospective cohort studies (PCSs) across the ODIN project (“Food-based solutions for optimal vitamin D nutrition and health through the life cycle”, FP7-613977), we analyzed the potential safety issues arising from vitamin D intakes and/or supplementation. These adverse consequences included high serum 25-hydroxyvitamin D (S-25(OH)D) concentrations (>125 nmol/L), high serum calcium concentrations, and vitamin D intakes in excess of the tolerable upper intake levels (ULs). In the RCTs (n = 3353, with vitamin D doses from 5–175 µg/day), there were no reported adverse effects. The prevalence of high S-25(OH)D was <10% when vitamin D supplements were administered, and <0.1% for fortified foods. Elevated serum calcium was observed among <0.5% in both administration types. No ODIN RCT participants exceeded the age-specific ULs. In observational studies (n = 61,082), the prevalence of high 25(OH)D among children/adolescents, adults, and older adults was <0.3%, with no evidence of adverse effects. In conclusion, high S-25(OH)D concentrations >125 nmol/L were rare in the RCTs and PCSs, and no associated adverse effects were observed.