Abstract Introduction The aim of the study was to evaluate the cytotoxicity, radiopacity, pH, and flow of a calcium silicate–based and an epoxy resin–based endodontic sealer, MTA Fillapex (Angelus, Londrina, PR, Brazil) and AH Plus (Dentsply, Konstanz, Germany), respectively. Methods Cytotoxicity, radiopacity, and flow evaluation were performed following ISO requirements. The pH level was measured at periods of 3, 24, 72, and 168 hours. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to check the Balb/c 3T3 cells viability at 1- to 4-week periods. Data were statistically analyzed by analysis of variance and the Tukey test with a significance level of 5%. Results In all tested periods, MTA Fillapex was more cytotoxic than AH Plus ( P < .05). Although AH Plus presented higher radiopacity than MTA Fillapex ( P < .05), both sealers showed minimum required values. MTA Fillapex presented alkaline pH in all experimental times, whereas AH Plus cement showed a slightly neutral pH and a flow significantly lower than that of MTA Fillapex ( P < .05). Conclusions Although MTA Fillapex was more cytotoxic than AH Plus, it showed suitable physicochemical properties for an endodontic sealer.