The aim of this study was to compare the biocompatibility of Endocem Zr® and ProRoot MTA® by histopathologic analysis in a canine model of pulpotomy. This study utilized 39 teeth of two beagle dogs. The exposed pulp tissues were treated by pulpotomy using ProRoot MTA (n=19) or Endocem Zr (n=20). After 8 weeks, the teeth were extracted and processed with hematoxylin-eosin staining for histologic evaluation. Most of the specimens in both groups developed a calcific barrier at the pulp amputation site and formed an odontoblast layer. However, some of the Endocem Zr specimens showed less calcific barrier formation with a greater inflammatory response and less odontoblast layer formation when compared with the ProRoot MTA specimens. ProRoot MTA and Endocem Zr specimens developed a calcific barrier; however, ProRoot MTA was more biocompatible than Endocem Zr.