Purpose: To evaluate the erosive effect of pediatric liquid medicinal syrups on primary and permanent enamel. Materials and methods: Eighty primary and permanent teeth were equally divided into eight subgroups (n=10), according to the immersion solutions: Depakine, Ventolin, Sansovit, and Artificial saliva. The immersion cycles  of the drugs were conducted under a 1-min agitation three times daily for 28 days. Enamel microhardness measurements were taken place at 0,7,14,21, and 28 days. The pH, titratable acidity, buffering capacity, and viscosity of the solutions were evaluated. A Scanning electron microscopy and statistical analysis of enamel microhardness measurements were assessed. Results: All the tested groups of the drugs had proven to produce significant demineralization of enamel after 28 days of exposure. At baseline,  the permanent enamel showed higher mean enamel microhardness values than primary teeth. Generally with all the tested drugs, the primary teeth showed more decrease in enamel microhardness than permanent but without significance. The primary group (028days), the highest decrease of enamel microhardness was recorded in Sansovit group, then Ventolin, followed by Depakine group without significant change between the  tested drugs, while in the permanent group, the highest decrease of enamel microhardness was recorded in Sansovit, then Depakine, followed by Ventolin group without significant change between the tested drugs. Kruskall Wallis test revealed a significant difference between tested drugs and control groups in both substrates. Conclusion: This study revealed that medicines used in the study could erode teeth even though the pH was above critical pH if it had high sugar content and viscosity. Sugar-free formulations have the ability to produce an erosive effect if they have low pH, high titratable acidity, high buffering capacity, and viscosity. This study showed that permanent teeth had higher mean enamel microhardness values than primary teeth, however no significant difference in the erosive potential of both types of teeth.