The development of xenon plasma focused ion-beam (Xe + PFIB) milling technique enables sitespecific sample preparation with milling rates several times larger than the conventional gallium focused ion-beam (Ga + FIB) technique. As such, the effect of higher beam currents and the heavier ions utilized in the Xe + PFIB system is of particular importance when investigating material properties. To investigate potential artifacts resulting from these new parameters, a comparative study is performed on transmission electron microscopy (TEM) samples prepared via Xe + PFIB and Ga + FIB systems. Utilizing samples prepared with each system, the mechanical properties of CrMnFeCoNi high-entropy alloy (HEA) samples are evaluated with in situ tensile straining TEM studies. The results show that HEA samples prepared by Xe + PFIB present better ductility but lower strength than those prepared by Ga + FIB. This is due to the small ion-irradiated volumes and the insignificant alloying effect brought by Xe irradiation. Overall, these results demonstrate that Xe + PFIB systems allow for a more efficient material removal rate while imparting less damage to HEAs than conventional Ga + FIB systems. The rapid development of micro-electromechanical systems (MEMS) and nano-electromechanical systems (NEMS), which utilize materials at the micron scale and below, has resulted in a growing number of potential applications in electronic devices 1. Mechanical properties are of particular importance for applications in M/NEMS as efforts seek to improve the functionality and reliability of advanced electronic devices. Continuing efforts have focused on understanding how the mechanical properties of these materials change with decreasing dimensions 2-6. To facilitate this understanding, in situ straining transmission electron microscopy (TEM) is commonly used to test the mechanical properties 7-10 and observe deformation mechanisms 11-17 of small-sized samples. In situ straining TEM allows for simultaneous structural characterisation and mechanical property testing 13,15,18 , providing opportunities for building direct relationships between microstructure, deformation mechanisms, and mechanical properties of small-sized materials. Sample preparation is of particular importance when studying small-sized materials in the TEM 19. Traditionally, these TEM samples are prepared using a focused ion-beam (FIB) with a gallium ion (Ga +) source to thin samples from bulk to ~100 nm 20-26. Despite technological advances, the material removal rates of Ga + FIB systems have remained too low for researchers hoping to increase sample preparation efficiency 27. To help facilitate more efficient sample preparation, researchers have developed FIB systems with alternative ion sources such as the Xe + plasma FIB (Xe + PFIB) 27. As an alternative to Ga + ions, Xe + PFIB systems utilize inert Xe gas as the milling media resulting in material removal rates around six times larger than for Ga + mills 27 , which enables the preparation of samples with larger dimensions. On...