SUMMARY This study evaluated the biocompatibility of contemporary bulk-fill resin-based composites (RBCs) including PRG (pre-reacted glass ionomer) materials based on the International Organization for Standardization 10993. In addition, the effect of composite thickness on cytotoxicity was also assessed. Two standard composites, two bulk-fill PRG RBCs, and three bulk-fill non-PRG RBCs were investigated. Block-shaped specimens of 2-mm and 4-mm thickness were cured with an irradiance of 700 mW/cm2 for 20 seconds with a light-emitting diode curing light and eluted with culture medium at 37°C for 24 hours. L929 mouse fibroblasts were exposed to extracts at varying dilutions (1:1, 1:2, and 1:10) for 24 hours. Analyses were performed to assess cytotoxicity, phase contrast microscopy, and quantitative cell viability. Among the bulk-fill RBCs, extracts of PRG materials resulted in the lowest cell viability. At 4-mm thickness, undiluted extracts of bulk-fill non-PRG RBCs had significantly higher cell viability than the standard composites. Chemical composition, specimen thickness, and testing concentrations of extracts had significant effects on cell viability and morphology. Cytotoxic effects of composites on cell viability were parallel with cell morphologic changes. Not all bulk-fill RBCs demonstrated high cell viability (>70%) at 4-mm thickness despite manufacturers' recommendations of bulk placement and curing.