OBJECTIVE: We investigated whether calcium plus vitamin D supplementation interacts with polymorphisms in the VDR gene promoter region to affect changes on maternal bone mass from 5 to 20 wk postpartum in Brazilian adolescent mothers. METHODS: Pregnant adolescents (14-19 y) randomly received calcium plus cholecalciferol (600 mg/d + 200 IU/d, n = 30) or placebo (n = 26) from 26 wk of pregnancy until parturition. Bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at total body, lumbar spine, total hip, and femoral neck were evaluated at 5 and 20 wk postpartum. Serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone concentrations were measured. Real-time polymerase chain reaction was used for genotyping rs7139166 (1521 pb G > C) and rs4516035 (1012 pb A > G). Interactions between supplementation and polymorphisms were adjusted for significant covariates. RESULTS: Changes in serum 25(OH)D from pregnancy to postpartum differed between supplemented and placebo groups for mothers carrying 1521 GG/1012 AA genotypes (P = 0.004). Only in the placebo group, mothers carrying 1521 GG/1012 AA had greater reduction in total BMD z score, femoral neck BMC, and BMD from 5 to 20 wk postpartum compared with those with 1521 GC/1012 AG (P < 0.05). In the placebo group, total hip BA decreased from 5 to 20 wk postpartum in adolescents with 1521 GG/1012 AA, but increased in those with 1521 GC/1012 AG (P < 0.05), in contrast to the supplemented group. CONCLUSION: Calcium plus vitamin D supplementation during pregnancy interacted with polymorphisms in the VDR gene promoter region affecting postpartum bone loss. The increased supply of calcium and vitamin D appeared to minimize postpartum bone loss particularly in adolescents with 1521 GG/1012 AA.