Introduction Mineral trioxide aggregate (MTA) is composed of calcium silicate cement and bismuth oxide added for radiopacity. The bismuth oxide in MTA has been reported to have a deleterious effect on the physical and chemical properties of the hydrated material. This study aimed to investigate the hydration mechanism of calcium silicate cement loaded with different radiopacifiers for use as a root-end filling material. Methods Calcium silicate cement loaded with barium sulfate, gold, or silver/tin alloy was hydrated, and paste microstructure was assessed after 30 days. In addition, atomic ratio plots of Al/Ca versus Si/Ca and S/Ca and Al/Ca were drawn, and X-ray energy dispersive analysis of the hydration products was performed to assess for inclusion of heavy metals. The leachate produced from the cements after storage of the cements in water for 28 days and the leaching of the radiopacifiers in an alkaline solution was assessed by using inductively coupled plasma. Results The hydrated calcium silicate cement was composed of calcium silicate hydrate, calcium hydroxide, ettringite, and monosulfate. Unhydrated cement particles were few. No heavy metals were detected in the calcium silicate hydrate except for the bismuth in MTA. Calcium was leached out early in large quantities that reduced with time. The barium and bismuth were leached in increasing amounts. Copper was the most soluble in alkaline solution followed by bismuth and barium in smaller amounts. Conclusions The bismuth oxide can be replaced by other radiopacifiers that do not affect the hydration mechanism of the resultant material.