Biomaterials used for medical application may cause some biological responses when applied to the body. Hence, biomaterials must be tested by various in vivo and in vitro test systems, before using on humans, according to different standardizations like ISO 19033. These tests are made to determine the biocompatibility of biomaterials and indicate their potential toxicity, irritation, and non-hemocompatibility. Furthermore, biomaterials must have similar mechanical properties as natural tissue has. For this reason, biomaterials are investigated in terms of mechanical properties such as tensile strength, elasticity and plastic deformation, viscoelasticity, failure, fracture, fatigue, and wear. This chapter seeks to elucidate certain principles and procedures of in vivo and in vitro test methods that determine biocompatibility and mechanical properties of biomaterials.