This in vivo study assessed calcium hydroxide's effect as a matrix carrier for recombinant human platelet-derived growth factor (rhPDGF) and enamel matrix protein (EMD) on pulp tissue healing following pulp capping. Intact premolar sites (n = 18) were included. Coronal access and pulpotomy were performed, and each tooth was exposed to the oral cavity for 1 hour before pulp capping was performed. Teeth were randomly assigned to one of the following pulp-capping groups (n = 6 each): Group 1 (CaOH2 only); Group 2 (CaOH2+EMD); and Group 3 (CaOH2+rhPDGF). Coronal access cavities were then sealed. Immediate preoperative, postoperative, and 4-month follow-up radiographs were taken. At 4 months, teeth were extracted atraumatically and histomorphometric and micro-CT analyses were performed. Group 1 showed formation of thin, uneven, highly porous dentin-like structure with tunnel defects (average thickness: 0.18 to 0.19 mm). Lack of continuity of the newly formed tissue and interrupted communication tunnels were seen between the pulpal space and pulp-capping material. Group 2 showed formation of highly dense, nonporous, even-thickness dentin-like structure obliterating multiple areas of the pulp space (average thickness: 0.9 to 0.94 mm). Abundant odontoblast lacunae were present in the pulp and structure. Group 3 showed formation of an inconsistent, uneven dentin-like structure that appeared highly porous (average thickness: 1.04 to 1.05 mm). It was without tunneling, and abundant odontoblastic lacunae were present. No statistically significant differences were found between Groups 2 and 3, but both were richer in newly formed dentin-like structure with more thickness than Group 1 (P .05). Addition of EMD to CaOH2 can result in multiple root canal calcifications, mostly in the coronal and apical thirds of the canals. The calcified tissue does not appear to resemble secondary dentin in form, shape, amount, or density. Addition of rhPDGF to CaOH2 may not cause root canal calcifications. The newly formed structure differs from secondary dentin in degree of mineralization, porosity, and density.