The fatigue properties of poly(methyl methacrylate) (PMMA) bone cement were significantly improved through 13.56-MHz radio frequency plasma treatments on the X-ray opaque powder and on the reinforcing fibers. For the plasma treatments of particle surfaces, a specially designed plasma reactor was used to modify the surfaces of the ZrO2 powder (X-ray opaque filler) and milled carbon fibers (reinforcing filler). The reactor chamber was designed to be rotated continuously to mix the particles during the plasma treatments to obtain uniformly treated particle surfaces. The surface peroxides resulting from the plasma treatments seemed to have a significant effect on the improvement of fatigue properties. The peroxides on the particles may yield free radicals by the reaction with the reducing agent (N,N-dimethyl-p-toluidine) in the bone cement mixture, which can initiate methyl methacrylate (MMA) polymerization. Through this graft polymerization process, the interfacial bond strength between the filler particles and the MMA matrix may be enhanced, resulting in efficient stress transfer from the matrix to the fillers. The best results of the fatigue tests were seen in the reinforced bone cement, which contained surface modified fillers, with hexamethyldisiloxane plasma, and with O2 plasma posttreatment.