Abstract: Currently, ion irradiation is commonly used to simulate neutron irradiation under specific conditions. Additionally, the nanoindentation testing system is extensively utilized for measuring the microscopic mechanical properties of materials that have been subjected to ion irradiation. One disadvantage of ion irradiation is its limited penetration depth, which prevents obtaining the corresponding macroscopic mechanical properties using conventional tensile experiments. In order to address this issue, microscopic mechanical properties are employed to predict macroscopic mechanical properties using empirical formulas or models. However, the acquisition of microscopic mechanical properties is influenced by numerous factors, such as surface conditions, the shape of the indenters, and the depth of indentation, which in turn can impact the accuracy of predictions. Consequently, it is crucial to conduct further comprehensive investigations to understand how these parameters affect the accuracy of predicted macroscopic mechanical properties. The shape of the indenters used in the nanoindentation testing system plays a crucial role as it directly influences the load-depth curves, thereby impacting the prediction of macroscopic mechanical properties. However, further comprehensive research is required to thoroughly investigate the specific influence of indenter radius on accurately predicting the macroscopic properties of irradiated materials. This paper investigated the impact of different spherical indenter radii (0.3, 1.0, and 10.0 μm) on predicting the Vickers hardness, yield strength, and elastic modulus of 3.5 MeV Fe²⁺ irradiated reduced activation ferritic/martensitic (RAFM) steel. The continuous stiffness measurement (CSM) method was employed in the TI950 nanoindentation testing system to acquire the microscopic properties. The experimental results show that the contact area measurement error results in an inverse size effect (ISE) in the irradiated samples regardless of variations in indenter radii and irradiation doses. In addition, due to the effects of irradiation-induced defects, such as dislocation loops, vacancies, and interstitial atoms, all the samples exhibit a pronounced hardening behavior as the irradiation dose increases from 0 to 1.43 dpa. However, as the irradiation dose increases, the hardening behavior gradually diminishes and ultimately transitions into irradiation softening. This can be attributed to the combined effects of defects induced by irradiation and structural recovery resulting from an increase in subgrain size. The hardness of RAFM steel gradually decreases with an increasing indenter radius under the same load and irradiation dose. For instance, the hardness is (9.15±0.60) GPa for 0.5 μm of indenter radius, while it reduces to (3.05±0.24) GPa as the indenter radius increases to 10.0 μm. Irrespective of the variations in irradiation dose, the predicted elastic modulus gradually increases with an increasing indenter radius. However, it is lower than the elastic modulus obtained from tensile experiments. This phenomenon occurs due to the increased ratio of elastic penetration depth to indentation depth with an increasing indenter radius. In contrast, the predicted yield strength gradually decreases as the radius of the indenter increases. The elastic modulus and yield strength both exhibit an increasing trend with an increasing irradiation dose for the same indenter radius. By comparing the unirradiated samples, the predicted yield strength and elastic modulus are in better agreement with the values obtained from the tensile experiments when the indenter radius increases to 10.0 μm. This investigation demonstrates that spherical indenters can effectively predict the macroscopic mechanical properties of ion irradiated RAFM steel. Furthermore, the larger the indenter radius, the closer to the values obtained from tensile testing.