This study compares CoCrMo particles generated by a high-energy ball milling method with those produced by the established Buchhorn method and with in vivo-generated wear particles from periprosthetic tissue. CoCrMo particles were produced utilization both methods. The particle size distribution was analyzed using laser diffraction, and the morphology was examined through scanning electron microscopy (SEM). Energy-dispersive X-ray spectroscopy (EDS) provided a qualitative analysis of the material composition. The high-energy ball milling method yielded CoCrMo particles with a D50 of 7.92 µm, a significantly smaller value than the D50 of 88.30 µm observed for Buchhorn particles. The SEM analysis demonstrated that the particles produced by the ball mill have a roundish, red blood cell-like and irregular shape, similar to that observed in particles generated in vivo. In contrast, the particles produced by the Buchhorn method exhibited a flake-like and irregular morphology. The ball mill particles displayed a tendency towards agglomeration, which was also observed in particles generated in vivo. In conclusion, the ball mill method produces CoCrMo particles that closely resemble natural wear particles in terms of size and morphology. These particles provide a superior model for biological testing in comparison to those produced by the Buchhorn method. Furthermore, the ball mill method offers advantages in terms of reproducibility and scalability, making it a promising alternative for the generation of CoCrMo particles for orthopedic research.