The production of functional parts, including those employed by the biomedical industry has been achieved a promising candidate in Fused Deposition Modelling (FDM). The essential properties of these biomedical parts which manufactured by additive manufacturing as compared to some other conventional manufacturing processes depend on structural and process parameters rather than material properties alone. Regarding to the evaluation the flexural strength of medical-grade, Polymethylmethacrylate PMMA has been received relatively very little investigation to date. PMMA is a biocompatible filament that be used in manufacturing of patient-specific implants such as dental prosthesis and orthopaedic implants. The proposed work explores the effect of three process parameters that vary with respect of three levels on the flexural strength. These levels can be specified by layer height (120, 200, 280 µm), infill density (40, 65, 90 %) and skewing angle (0º, 45º, 90º) on the flexural strength of medical-grade PMMA. Maximum and minimum flexural strength that be obtained in this work about (93 and 57 MPa) respectively. The analysis of variance (ANOVA) results shows that the most effective factor is the layer height followed by infill density. The flexural strength rises significantly with decreases layer height and the skewing angle is in zero direction. The process parameters have been optimized through utilizing of genetic algorithms. The optimal results that emerged based on genetic algorithm technique are approximately (276 μm) as layer height, (46 %) infill density and skewing angle (89 º) which maximize the flexural strength to (97 MPa) at crossover for ten generation.