Mineral trioxide aggregate (MTA) is the most frequently used repair material in endodontics, but the long setting time and reduced mechanical strength in acidic environments are major shortcomings. In this study, a novel sol-gel-derived calcium silicate cement (sCSC) was developed using an initial Ca/Si molar ratio of 3, with the most effective mixing orders of reactants and optimal HNO
3
catalyst volumes. A Fourier transform infrared spectrometer, scanning electron microscope with energy-dispersive X-ray spectroscopy, and X-ray powder diffractometer were used for material characterization. The setting time, compressive strength, and microhardness of sCSC after hydration in neutral and pH 5 environments were compared with that of MTA. Results showed that sCSC demonstrated porous microstructures with a setting time of ~30 min, and the major components of sCSC were tricalcium silicate, dicalcium silicate, and calcium oxide. The optimal formula of sCSC was sn200, which exhibited significantly higher compressive strength and microhardness than MTA, irrespective of neutral or pH 5 environments. In addition, both sn200 and MTA demonstrated good biocompatibility because cell viability was similar to that of the control. These findings suggest that sn200 merits further clinical study for potential application in endodontic repair of perforations.