This in vivo study assessed the effect of mineral trioxide aggregate (MTA) as a matrix carrier for recombinant human platelet-derived growth factor (rhPDGF) and enamel matrix protein (EMP) on pulp tissue healing following pulp capping. Eighteen intact human premolars scheduled for extraction were included. Coronal access and pulpotomy were performed, and each tooth was left 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 (MTA only); Group 2 (MTA+EMP); or Group 3 (MTA+rhPDGF). Coronal access cavities were then sealed. Immediate preoperative, postoperative, and 4-month follow-up radiographs were taken. At 4 months, the teeth were extracted atraumatically, and histomorphometric and micro-computed tomography (μCT) analyses were performed. Group 1 showed a thin, uneven, irregular dentin-like structure. Its average thickness was 0.3 ± 0.084 mm measured histologically and 0.29 ± 0.091 mm measured by μCT. Group 2 showed of a nonporous, even-thickness dentin-like structure with multiple root-canal obliterations. Highly dense, atubular dentin-like structures associated with presence of odontoblastic lacunae were seen. The structure's average thickness was 0.87 ± 0.09 mm (histologically) and 0.81 ± 0.17 mm (μCT). Group 3 showed a thick and complete 3D continuous seal of newly formed dentin-like structure covering the pulpal space. It resembled secondary dentin in form, porosity, and tubular structural organization, and its average thickness was 0.94 ± 0.02 mm (histologically) and 0.91 ± 0.09 mm (μCT). Groups 2 and 3 showed higher amounts of newly formed dentin-like structure, that was also thicker, than Group 1 (P .05). No statistically significant differences in structure thickness were found between Groups 2 and 3. The nature of the structure can differ if rhPDGF or EMP is added to MTA for pulp-capping purposes. Combination of rhPDGF and MTA resulted in a newly formed structure resembling secondary dentin, whereas a combination of EMP and MTA produced a nonporous, highly dense dentinal-like structure associated with significant root-canal obliterations.