The biocompatibility and strength retention of a Mg-Ca-Zn alloy were studied to evaluate its efficacy for osteosynthesis applications. Mg-Ca-Zn alloy and self-reinforced poly l-lactide (SR-PLLA) bone screws were implanted into New Zealand rabbits for radiography analysis, micro computed tomography analysis, histomorphometry, hematology, serum biochemistry, histopathology, and inductively coupled plasma mass spectrometry analysis. Bending and torsion tests were performed on intact specimens to find the initial mechanical strength of these Mg-Ca-Zn alloy bone screws. Strength retention of the Mg-Ca-Zn alloy implants were calculated from in vivo degradation rates and initial mechanical strength. Based on the animal study, Mg-Ca-Zn alloy bone screw showed absence of subcutaneous gas pockets, characteristic surface erosion properties, faster degradation rate than SR-PLLA bone screw, normal reference range of hematology and serum biochemistry, better histopathological response than SR-PLLA bone screw, and stable concentrations of each constituent element in soft tissues surrounding the implants. The initial strength and strength retention of Mg-Ca-Zn alloy were compared with those of various biomaterials. The initial strength of Mg-Ca-Zn alloy was higher than those of biostable and biodegradable polymers. The strength retention of Mg-Ca-Zn alloy bone screws was similar to those of biodegradable polymer. Therefore, this Mg-Ca-Zn alloy represents an excellent biodegradable biomaterial candidate for osteosynthesis applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.