The aim of the present study was to compare the efficacy of two pulp capping materials; Iodoform/dexamethasone acetate containing material (Pulpotec) and Mineral Trioxide Aggregate (MTA) in vital pulp therapy, as regard to their physical properties and for the biological evaluation, both materials were used in addition to the calcium hydroxide. Materials and Methods: For the characterization of Pulpotec, x-ray fluorescence spectrometer (XRF) and Fourier transform infra-red spectroscopy (FTIR) were used. The pH was measured during setting by using fresh mix of both material and a pHmeter. For the measurement of pH after setting, the calcium and phenol leached out, five cylindrical specimens of each material were prepared, using a special mold and suspended in distilled water. The storage water was collected and replaced after different time intervals. The pH was measured by a pHmeter, the released Ca ions was detected by an atomic absorption spectrophotometry and the leached out phenolic compounds were detected using a spectrophotometer. The solubility and disintegration of both materials were measured in simulated dentinal fluid at different time intervals by calculating the % of disintegration. The tissue reaction in contact with both materials was assessed to detect the dentin bridge formation. Four male white rabbits were used with a total number of 16 teeth and Ca(OH)2 was used as a control. Results: The X-Ray fluorescence analysis of the pulpotec powder showed different elements and oxides where (ZnO) represented the highest percentage, while the (P2O5) showed the lowest one. From the FTIR spectral curves, we concluded that a chemical reaction has occurred and a new complex compound was formed. During setting, Pulpotec had a significantly lower pH values than MTA, while after setting, both materials showed the same pattern of neutrality. For the leached calcium ions MTA showed higher amount of Ca ions than Pulpotec. The leached out phenolic compounds reached a high level gradually decreased at the end of the study. Pulpotec showed higher solubility than MTA. The histological evaluation of the tested materials revealed the presence of a dentine bridge in both materials. For the calcium hydroxide treated group, there was an absence of inflammation with globules of calcifications. Pulpotec H&E sections showed hyalinization of the pulp tissue with a newly formed eosinophilic dentinoid material and a distinct dentine bridge. A clear dentine bridge was also detected with different- sized globules of calcifications. Conclusions: The chemical composition and the pH of the pulp capping materials have a role on the pulp tissue and the dentine bridge formation. The phenol and formaldehyde are considered to be responsible of pulp hyalinization. Long term solubility of calcium containing materials is considered negligible in simulated dentinal fluid. Calcium containing materials allow the formation of globules of calcification when applied on pulp tissue.