Purpose: To evaluate the effect of adding Al2O3, SiO2, and TiO2 nanoparticles in ratios of 1, 3, and 5 wt% to different acrylic resins on flexural strength. Materials and Methods: A total of 210 specimens were prepared in 30 groups (n = 7/group) (Control, 1% Al2O3, 3% Al2O3, 5% Al2O3, 1% SiO2, 3% SiO2, 5% SiO2, 1% TiO2, 3% TiO2, 5% TiO2). The specimens were polished with 200-, 400-, and 600-grit abrasive paper to provide a standard surface before testing and then suspended in distilled water for 30 days. Flexural strength was measured via three-point bending tests. Subsequently, SEM analysis was performed for one specimen from each group. Homogeneity of data was assessed by Kolmogov–Smirnov test followed by two-way ANOVA and Tukey HSD tests (α = 0.05). Results: There was a significant increase in the flexural strength of polymethylmethacrylate (PMMA) after addition of 1% nanoparticles in both heat-polymerized and autopolymerized acrylic resins (p ˂ 0.05). The flexural strength values of the groups to which Al2O3 and TiO2 nanoparticles were added exceeded those of the group with SiO2 addition (p ˂ 0.05). The electron microscopy images revealed that the nanoparticles were more homogeneously dispersed in PMMA with higher flexural strength. Conclusions: The mechanical properties of PMMA can be improved by the addition of nanoparticles to PMMA; however, the flexural strength values of PMMA decrease with the addition of nanoparticles at higher percentages (3-5%). Hence, the ideal filler ratio corresponds to 1%.