AIM: To investigate the pulpal response to direct pulp capping in healthy human teeth with mineral trioxide aggregate (MTA) as against calcium hydroxide cement (Dycal) as control. METHODOLOGY: Twenty healthy human third molars had iatrogenic pulpotomy and direct pulp capping with MTA. Another 13 teeth were capped with Dycal as controls. The teeth were restored, with IRM, clinically reviewed and extracted after a number of pre-determined intervals (1 week, 1 month and 3 months). The specimens were fixed, decalcified, subdivided axially into two halves in the oro-buccal (lingual-buccal) plane, embedded in plastic, serial sectioned and evaluated qualitatively and quantitatively by correlative light and transmission electron microscopy with appropriate statistical evaluation of the quantitative data. RESULTS: Iatrogenic pulpal wounds treated with MTA were mostly free from inflammation after 1 week and became covered with a compact, hard tissue barrier of steadily increasing length and thickness within 3 months following capping. Control teeth treated with Dycal revealed distinctly less consistent formation of a hard tissue barrier that had numerous tunnel defects. The presence of pulpal inflammation up to the longest observation period (3 months) after capping, was a common feature in Dycal specimens. CONCLUSIONS: The MTA was clinically easier to use as a direct pulp-capping agent and resulted in less pulpal inflammation and more predictable hard tissue barrier formation than Dycal. Therefore, MTA or equivalent products should be the material of choice for direct pulp capping procedures instead of hard setting calcium hydroxide cements.