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The effect of microstructure evolution on tensile fracture behavior of biomedical Mg-2Zn-1Nd-0.6Zr alloy was investigated using OM, EPMA, SEM, TEM, EBSD and Nano-indentation. Results indicated that the as-cast Mg-2Zn-1Nd-0.6Zr alloy composed of α-Mg matrix, netlike and granular Mg35Zn40Nd25 (T3) secondary phases. Volume fraction of secondary phases in homogenized and solution-treated alloys decreased from 7.2% to 4.6% and 0%, respectively, whilst elements distributed more uniform and grain did not grow significantly. Grain size of extruded + aged alloy decreased from 110 μm to 12 μm, forming band-shaped phases with size of 0.2–1.5 μm and high-density nanoscale precipitates with size of 5–20 nm. Moreover, Mg35Zn40Nd25 phase exhibited higher elastic modulus (57.5 GPa) and hardness (1.47 GPa) than all matrices. With the change of phase content, phase morphology and grain size, the fracture mode of as-cast, homogenized, solution-treated and extruded + aged alloys during the conventional tensile test changed from intergranular fracture to quasi-cleavage fracture, transgranular fracture and ductile fracture. In addition, the effect of reduced surface integrity on cracking susceptibility could be ranked in the order of as-cast > homogenized > solution-treated > extruded + aged. Keywords: Mg alloy, Biomedical, Microstructure evolution, Pre-immersion, Tensile fracture