During the last few decades, knowledge about growth factors and their function has increased. However, little is known about the interaction of these factors during bone growth and fracture healing. In vitro studies have shown a higher rate of cell proliferation and cell metabolism after the use of IGF-I and TGF-beta1 in combination, as compared to the single use of these factors. The purpose of this study was to investigate a possible synergistic effect of these growth factors in vivo, using a fracture model. A midshaft fracture of rat tibia (n = 84) was intramedullary stabilized with poly(D,L-lactide)-coated or uncoated titanium K-wires. The growth factors IGF-I and TGF-beta1, singly or in combination, were incorporated in the coating and continuously released during fracture healing. 28 days after fracture, we performed mechanical tests and histomorphological analyses. We found a greater stimulating effect of IGF-I on fracture healing than of TGF-beta1. The combined application of both growth factors resulted in a significantly higher maximum load and torsional stiffness than the use of only one of them. The histomorphometric analyses showed an increase in remodeling of the fracture callus in this group with less cartilaginous and more mineralized tissue than in the other groups. Both growth factors seem to have a synergistic effect on fracture healing in this model.