Objectives: To evaluate the effect of microwave postpolymerization heat treatment and water storage time on the cytotoxicity of denture base and reline acrylic resins. Method and Materials: Sample disks of 6 acrylic resins were fabricated under aseptic conditions (Kooliner, GC; Tokuyama Rebase II, Tokuyama Dental; New Truliner, Bosworth; Acron MC, GC; Lucitone 550, Dentsply; QC 20, Dentsply). The denture base acrylic resin samples were stored in water for 24 and 48 hours at 37°C. The fabricated samples were further subdivided into 2 groups: (1) samples without heat treatment and (2) samples treated in a microwave. The 3H-thymidine incorporation test was used to determine the cytotoxicity of the materials. The data were statistically analyzed using the incomplete 3-way ANOVA and Tukey HSD tests (P .05). Results: Microwave postpolymerization heat treatment improved the biocompatibility of Tokuyama Rebase II. Tokuyama Rebase II without heat treatment and Acron MC in both experimental groups were graded as slightly cytotoxic in the group without water storage. The other resins were graded as noncytotoxic. After 24 hours of immersion in water, all materials were graded as noncytotoxic. After water storage for 48 hours, Acron MC without heat treatment and QC 20 in both experimental groups were graded as slightly cytotoxic. Lucitone 550 was graded as noncytotoxic in all experimental groups. Conclusion: Microwave irradiation may be considered an alternative to reduce the cytotoxicity of Tokuyama Rebase II. Dental practitioners should choose Lucitone 550 processed with terminal boiling stage. Keywords: biocompatibility, cell viability, microwave, polymethyl methacrylate