Scaffolds prepared from biodegradable polyurethanes (PUR) have been investigated as a supportive matrix and delivery system for skin, cardiovascular, and bone tissue engineering. In this study, we combined reactive two-component PUR scaffolds with lovastatin (LV), which has been reported to have a bone anabolic effect especially when delivered locally, for effective bone tissue regeneration. To incorporate LV into PUR scaffolds, LV was combined with the hardener component before scaffold synthesis. The PUR scaffolds containing LV (PUR/LV) demonstrated a highly porous structure with interconnected pores, which supported in vitro cell attachment and proliferation and in vivo osteoconductive potential. The PUR/LV scaffolds showed sustained release of biologically active LV, as evidenced by the fact that LV releasates significantly enhanced osteogenic differentiation of osteoblastic cells in vitro. A study of bone formation in vivo using a rat plug defect model showed that the PUR/LV scaffolds were biocompatible. Further, locally delivered LV enhanced new bone formation in the PUR scaffolds at week 4, while there were no obvious effects at week 2. These results suggest that the sustained LV delivery system from PUR scaffolds is a potentially safe and effective device for bone regeneration.