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Inconel X-750 is a Ni-rich super-alloy with high strength and creep resistance. In CANDU reactors, it is used as tight fitting fuel channel annulus spacers (in the form of a spring). Unlike other reactor designs, the CANDU reactor has a high thermal neutron flux spectra, which, combined with the higher thermal neutron cross section of 58Ni results in an enhancement of the radiation damage and the internal production of helium and hydrogen. In recent years, it has been observed these spacers are losing ductility and strength following irradiation. The mechanical property evolution of these components is dependent on the irradiation temperature and dose. The primary degradation mechanism remains unclear, and thus provides the focus of this investigation. Inconel X-750 irradiated to these extreme conditions have never been examined prior to this research. The microstructural characterization included in this dissertation include: fractography, microstructural evolution and mechanical property evolution. The discussion of the microstructural evolution is focused on the characterization of helium bubbles. The bubbles form homogeneously in the matrix and aligned along sinks such as dislocations, grain boundaries and precipitates. Electron energy loss spectroscopy (EELS) has been used to probe individual nano-sized bubbles to provide insights into the helium density, helium-to-vacancy ratio, and pressures through the use of a hard sphere equation of state (HSEOS). In addition to understanding the influence of irradiation on helium bubbles, the evolution of secondary strengthening precipitates, gamma prime, are of interest as these precipitates play an important role on the strength and creep resistance of the unirradiated material. The stability of these precipitates with irradiation is thus an important factor to consider with respect to the microstructural degradation. The microstructure is linked to the mechanical properties via microhardness testing on adjacent material. A major contribution to this field is an approach to utilize a focused ion beam (FIB) and transmission electron microscopy (TEM) to perform high ii resolution failure analysis of an intergranular fracture surface. Although this technique is not altogether revolutionary, the application of this approach towards post irradiation examination of heavily irradiated Inconel X-750 is unique. This approach provides direct evidence of likely degradation mechanisms, and provides insights for future post irradiation failure analysis for other applicable nuclear components. Working with ex-service material creates some complications with respect to known and unknown variables making it difficult to assess all factors responsible for material degradation. To compliment the program, a controlled proton irradiation program has been performed to gain additional insights into in the effects of irradiation on the microstructure and mechanical property evolution of Inconel X-750, due to the inability to perform controlled experiments with in-service reactor components. In addition to providing a detailed analysis of a CANDU component’s degradation, this study provides comprehensive information on irradiation damage processes applicable to other reactor core components. Thesis Doctor of Philosophy (PhD)