Mineral trioxide aggregate (MTA) has shown good biocompatibility in several studies. In the present study, the genotoxic and cytotoxic effects of calcium enriched mixture (CEM) were evaluated compared with MTA using MTT and single-cell gel (comet) assays with serial ascending concentrations (0 to 1,000 µg/mL) of tested materials. Cytotoxicity data indicated that there is no significant difference between CEM and MTA at all concentrations except for the full concentration (1,000 µg/mL); CEM had lower cytotoxicity. Genotoxic effects were more evident with CEM at concentrations of 15.6 and 250 µg/mL; however, was less than that of MTA at concentrations of 500 and 1,000 µg/mL. The cytotoxicity and genotoxicity effects of the two experimental groups generally increased with consistency. Under the conditions of this study, CEM is biocompatible in terms of cyto- and genotoxicity. It appears to be an alternative to MTA as an endodontic biomaterial offering several advantages.