Ion irradiation and annealing experiments were performed on Zr52.5Cu17.9Ni14.6Al10Ti5 “BAM-11” bulk metallic glass (BMG) specimens to evaluate their irradiation- and temperature-induced microstructural and mechanical property evolution. For the ion irradiations, samples were exposed to 9 MeV Ni3+ ions to a midrange (∼1.5 nm depth) dose of 10 displacements per atom (dpa) at temperatures ranging from 25 to 360 °C. A separate set of samples were annealed at 150 °C, 200 °C and 300 °C with respective heating times of 96, 72, and 48 h. Bulk X-ray diffraction (XRD) and transmission electron microscopy (TEM) characterization revealed that the alloy did not crystallize during irradiation up to 290 °C, although partial crystallization occurred at 360 °C throughout the unirradiated and irradiated regions of the sample. Transmission electron microscopy (TEM) characterization suggested that some of the irradiated region retained an amorphous structure, supporting the idea of partial crystallization. XRD analysis revealed that the crystallization which occurred in the sample irradiated at 360 °C was caused by thermal effects, and not irradiation displacement damage, and may be due to slight impurity contamination in the ingot. Nanoindentation experiments showed that only a slight amount of hardening was observed in the specimen irradiated at room temperature and 290 °C. However, significant hardening occurred in the sample irradiated at 360 °C (∼18% increase) as well as the unirradiated annealed specimens. For the sample irradiated at the highest temperature, the substantial increase in hardness was attributed to the partial crystallization of the alloy due to thermal, rather than irradiation effects. Overall, the results of the XRD and nanoindentation characterizations indicate good stability during irradiation at 25–290 °C but suggest that the BAM-11 BMG is not suitable for irradiation environments where temperatures exceed 300 °C for prolonged periods of time. Three different extrapolation models were employed to study how irradiation and annealing modify the indentation size effect (ISE) in the BAM-11 BMG. The poor linear fitting, as exhibited by all of the underlying equations, indicate that a new ISE model is needed to quantify nanoindentation mechanical properties in BMGs.