Objectives <p>TheraCal PT is a novel resin-modified calcium-silicate material introduced for vital pulp therapies. This study aimed to investigate the inflammation and hard tissue formation after pulpotomy treatment with Biodentine and TheraCal PT in inflamed or healthy rat molar teeth.</p> Methods <p>This study consisted of six groups (<i>n</i> = 12, 72 teeth): negative control-no preparation (NC); positive control (PC); Biodentine-pulpitis teeth (BD-P), TheraCal PT-pulpitis teeth (TPT-P), Biodentine-healthy teeth (BD-H), TheraCal PT-healthy teeth (TPT-P). For PC, BD-P and TPT-P groups, teeth were induced with lipopolysaccharide for 12&#xa0;h. Pulpotomy procedure was performed with Biodentine and TheraCal PT. Eight weeks later, pulpal inflammatory cell infiltration and hard tissue formation were evaluated by histological analysis. Pearson’s chi-square test was performed.</p> Results <p>There were significant differences among groups for inflammation and hard tissue formation (<i>p</i> &lt;.05). PC group showed moderate to severe inflammation. Biodentine groups showed lower inflammation scores than TheraCal PT groups. Pulpitis-induced groups showed higher inflammation scores than healthy groups. In Biodentine groups, complete hard tissue formation was higher than incomplete hard tissue formation. TheraCal PT groups showed mostly incomplete or no hard tissue formation. Pulpitis-induced groups showed inferior hard tissue formation scores than healthy groups.</p> Conclusions <p>TheraCal PT as a pulp capping material and inflamed pulp as a pre-treatment tooth condition showed inferior results in pulpotomy treatment. Biodentine exhibited favorable inflammatory pulpal responses and thicker hard tissue formation than TheraCal PT.</p> Clinical relevance <p>The novel resin-modified calcium-silicate material showed inferior inflammatory cell infiltration and hard tissue formation results in pulpotomy-treated teeth with irreversible pulpitis.</p>