Background: Strontium ranelate is used to treat osteoporosis. Calcium (Ca) and strontium (Sr) have common chemical features and are absorbed by the same pathways. Vitamin D has a main role in calcium intestinal absorption. The aim of this study was to investigate whether vitamin D status is a determinant of strontium ranelate absorption. Methods: Twenty-five patients with vitamin D deficiency (25(OH)D!50 nmol/l) and 25 with vitamin D sufficiency (25(OH)DO75 nmol/l) underwent a 4-h oral Sr overload test. Sr absorption was evaluated as the fraction of absorbed dose and the area under the curve. After the baseline overload test, the deficient patients were treated until reaching sufficient vitamin D levels (25(OH)DO75 nmol/l) and the test was repeated. Results: Changing vitamin D status from deficient to sufficient resulted in a significant increase in 1,25(OH) 2 D (24.97G 4.64!34.62G9.14 pg/ml, P!0.001) and a reduction in parathyroid hormone (73.87G37.50!58.24G20.13 pg/ml, PZ0.006). Nevertheless, no differences were found in the parameters used to evaluate Sr absorption between the vitamin D deficient and sufficient groups. In addition, vitamin D3 replacement in the deficient group did not result in enhanced Sr absorption. Conclusion: Vitamin D status did not interfere with strontium ranelate absorption. Taking into account the benefits of adequate vitamin D status in osteoporotic patients, we strongly recommend the treatment of vitamin D deficiency. However, the data demonstrate that such treatment does not enhance strontium ranelate absorption in patients with mild deficiency.