BACKGROUND The forces exerted on teeth and prostheses during mastication are repeated and dynamic, resulting in fatigue damage to dental prostheses. Most fractures of dental restorations are fatigue failure. The 4-point bend fatigue behavior of Co-Cr-Mo-W alloys manufactured by investment casting (CAST) and selective laser melting (SLM) has received little attention. OBJECTIVE The purpose of this in vitro study was to evaluate the 4-point bend fatigue property of dental Co-Cr alloys and determine the relationship between microstructure and the 4-point bend fatigue property of Co-Cr alloys created by traditional casting and SLM. These can guide the use of Co-Cr alloy in dentistry. METHODS Co-Cr-Mo-W alloys were fabricated with a dimension of 45×2×2 mm by investment casting and SLM. The 3-point bend test measured the ultimate bend strength with 3 specimens in each group. The 4-point bend fatigue test evaluated the fatigue life under various stresses, with 6 specimens in each group. The specimens were mechanically ground, polished, and electrochemically etched. Scanning electron microscopy was used to identify the microstructures of both etched specimens and fracture surfaces. X-ray diffraction investigations were used to determine the phases. Significant differences in the bend strength were analyzed by using the independent samples t test (α=.05), and the fatigue test was analyzed with ANCOVA (α=.05). RESULTS The mean ±standard deviation bend strength of SLM specimens was 1837 ±3 MPa, higher than the 1200 ±6 MPa for CAST specimens (P<.05). The maximum bend stress of the SLM specimens without fatigue failure was 735 MPa, which was statistically higher than the 394 MPa for CAST specimens (P<.05). The microstructure characteristics of the SLM alloy contributed to its excellent fatigue performance. In SLM alloy, the γ phase constituted the majority with some ε and Laves phases, while the cast alloy possessed higher ε and Laves phases. The grains of SLM alloy were equiaxed and fine, and the second phases were fine and dispersive. In contrast, the cast alloy possessed clear dendrites, and the second phases were sizable. CONCLUSIONS The SLM dental Co-Cr-Mo-W alloy had statistically better 4-point bend fatigue properties than cast alloy, which was associated with an improved microstructure.