To assess the physicochemical properties of AH Plus, GuttaFlow 2, GuttaFlow BioSeal, and MM Seal, five samples of each root canal sealer were evaluated to determine their setting time (ST), dimensional change (DC), solubility (SL), flow (FL), and radiopacity (RD) according to American National Standards Institute/American Dental Association (ANSI/ADA) Specification 57. The distilled and deionized water obtained from the SL test were subjected to atomic absorption spectrometry to observe the presence of Ca2+, K+, and Na+ ions. Statistical analysis was performed by using one-way ANOVA and Tukey-Kramer tests (p < 0.05). The following results were obtained: ST (min) (AH Plus 463.6 ± 13.22; GuttaFlow 2 24.35 ± 2.78; GuttaFlow Bioseal 17.4 ± 0.55; MM Seal 47.60 ± 4.39), DC (%) (AH Plus 0.06 ± 0.12; GuttaFlow 2 -26.06 ± 1.24; GuttaFlow Bioseal 2.10 ± 1.47; MM Seal 8.47 ± 2.41), SL (%) (AH Plus 0.41 ± 0.21; GuttaFlow 2 5.13 ± 4.11; GuttaFlow Bioseal 3.03 ± 1.05; MM Seal 0.94 ± 0.17), FL (mm) (AH Plus 36.42 ± 0.40; GuttaFlow 2 36.44 ± 0.05; GuttaFlow Bioseal 35.4 ± 0.03; MM Seal 52.75 ± 0.60), and RD (mmAl) (AH Plus 7.52 ± 1.59; GuttaFlow 2 6.85 ± 0.14; GuttaFlow Bioseal 7.02 ± 0.18; MM Seal 3.32 ± 0.90). ST, DC, SL, FL, and RD showed statistical differences among the root canal sealers (p < 0.05). As AH Plus showed the lowest DC and SL values (p < 0.05), the findings indicate that this sample is the only sealer conforming to ANSI/ADA standards.