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Background: Dental erosion is an irreversible damage to hard tissues in the mouth due to acid dissolution not induced by microorganisms. Oral medications contributed to the etiology of dental erosion. Among these medications, antihistamine-containing syrups were reported to have a considerable erosive effect on hard dental tissues. Objective: The objective was to evaluate the effect of Zamzam water on the microhardness of primary tooth enamel after erosion induced by Claritin™ syrup. Materials and Methods: The present in-vitro study was conducted on 25 primary central incisor teeth. The labial surfaces of the specimens were prepared for microhardness testing. Baseline microhardness was measured first, then the samples were submerged in the erosive agent Claritin™ syrup, for 30 min every 12 h for 12 days. Thereafter, all the teeth were placed in Zamzam water for 30 min every 12 h for 12 days. The microhardness was measured by the Vickers hardness tester and expressed as Vickers microhardness value (VH). The measurements were completed three times for the same sample: baseline, after erosion, and after Zamzam treatment. Data were analyzed statistically using one-way repeated analysis of variance (ANOVA) followed by Tukey’s post hoc test. Results: The primary teeth included in this study showed a significant increase in their surface microhardness after Zamzam water treatment; the mean value of VH was increased from 33.12 ± 1.62 to 89.32 ± 8.52 (P-value