OBJECTIVE: To investigate the pulpal response to direct pulp capping in healthy human teeth with Portland cement (PC) as against mineral trioxide aggregate (MTA) as control.METHODS: Forty healthy human third molars indicated for extraction were randomly divided into two groups: PC and MTA. The teeth had iatrogenic pulp exposed and direct pulp capping with PC or MTA. After 1, 7, 14 and 21 days, the teeth were extracted and prepared for histological examination and bacterial detection. The Mann-Whitney test was applied for statistical analysis (p < 0.05).RESULTS: The MTA presented higher capacity to form of dentin bridges at 14- and 21-day intervals (p < 0.05). However, no significant statistical difference was found between the groups at all evaluated intervals (p > 0.05) for the response variables of inflammatory cells, soft tissue organization and bacterial staining.CONCLUSION: The PC has a biocompatibility equivalent to the MTA but with a lower capacity to form of dentin bridges. Therefore, MTA should be the material of choice for direct pulp capping.