RGDS (Arg-Gly-Asp-Ser) is immobilized on poly(L-lactic acid) (PLLA) with ozone oxidation and the addition of an intermediate reactant, acryl succinimide (ASI) to promote the grafting efficiency. A DPPH (2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl) assay has revealed that the peroxide concentration can be controlled by adjusting the ozone treatment time. The immobilization of ASI is verified by elemental analysis. The peptide concentrations are in the effective order, as shown by means of high performance liquid chromatography (HPLC), and the grafting efficiency is proven to be relatively high compared with the previous studies. The culture of rat osteosarcoma 17/2.8 (ROS), osteoblastic-like cells, demonstrates that the grafting of RGDS can enhance the attachment and osteogenesis of ROS cells on PLLA. With the addition of ASI, the cultured ROS cells express normal function in proliferation and mineralization. From in vivo experiments, ASI immobilized on the surface is shown to be biocompatible. These results lead to the conclusion that the ozone treatment with the intermediate reactant ASI is an efficient, biocompatible, and easily controllable procedure to modify PLLA. Furthermore, the immobilization of RGDS in significant amounts following the ozone oxidation could further promote the biocompatibility and the osteoinduction of PLLA.