tisIntroduction: The purpose of this study was to examine and compare the capacity of a mineral trioxide aggregate-based (MTA) root canal sealer with two resin self-etch root canal sealers (RealSeal SE and MetaSEAL) to induce oxidative stress and apoptosis on human fibroblasts, MRC-5 cells. Methods: For cytotoxicity testing, cells were exposed to the selected test materials then evaluated after 24 hours and 7 days using [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] MTT assay. The extent of the apoptosis was determined using propidium iodide and Annexin V-FITC double staining. Results: MTA was significantly the least toxic material at both observation times (P 0.05) and the toxicity of RealSeal SE significantly decreased after 7 days, showing no significant difference to MTA (P 0.05). MetaSEAL was significantly the most toxic material at both observation times (P 0.05), and time had no significant effect on it (P > 0.05). RealSeal SE induced the highest number of apoptotic cells as well as apoptotic/necrotic cells, than both MTA and MetaSEAL. Conclusions: The cytotoxicity of RealSeal SE significantly decreased with time to show MTA's mild cytotoxicity on viable cells. While time had no effect on the toxicity of MetaSEAL, this root canal sealer displayed severe toxic effects on viable cells. Keywords: apoptosis, cytotoxicity, flow cytometry, MetaSEAL, MTA, MTT assay, oxidative stress, RealSeal SE