Transforming growth factor-beta induced (TGFBI) and periostin are two closely related proteins in structure as well as in function. A previous study found that periostin positively regulates bone size. Here, we hypothesize that TGFBI has a similar function in bone development. To test this hypothesis, we employed TGFBI-deficient mice, which were generated by targeted disruption of the TGFBI gene. We bred these mice with C57BL/6J mice to generate homozygous TGFBI-deficient (TGFBI(-/-)) mice and homozygous wild-type littermates. All mice were raised to 12 weeks of age. Bone mass parameters were determined by PIXImus and micro-CT, bone strength parameters by three-point bending, and bone formation and resorption parameters by histomorphometry. We found that targeted disruption of TGFBI led to reduced body size, bone mass, bone size, and bone strength. This indicates that, like periostin, TGFBI also positively regulates bone size and that changes in bone size affect bone strength. Furthermore, there was also a significant decrease in periosteal, but not endosteal, bone formation rate of cortical bone in TGFBI(-/-) mice, suggesting that the observed effect of TGFBI on bone mass and bone size was largely caused by the effect of TGFBI on periosteal bone formation.