The European Union Medical Device Regulation (EUMDR 2017/745) and US FDA require orthopedic implants manufacturers to meet the performance testing requirements that are essential for safe clinical use of the implants. This book chapter provides an overview of the importance of the preclinical testing considering the European Union and US FDA expectations. With advancement in the additive manufacturing methods, there are several risks that may arise from the 3D printing manufacturing methods and post-processing of the additively manufactured implants; the current regulations are strictly focusing on risks associated with these technologies. Manufacturers must ensure conformity with the general safety and performance requirements outlined in Annex I of the MDR. This encompasses stringent criteria for biocompatibility, mechanical stability, and material safety, necessitating comprehensive testing and validation. Both the EU MDR and FDA have rigorous testing requirements for 3D-printed orthopedic implants to ensure patient safety and device effectiveness. Manufacturers must adhere to these regulations, providing comprehensive evidence that their devices meet all necessary standards and requirements.