Aim: The purpose of this study was to determine the three most commonly prescribed antibiotics in a group of Egyptian Pediatricians. These antibiotics were evaluated regarding their effect on marginal adaptaion of glass ionomer restoration. Materials and Method: First, a questionnaire was conducted in two large hospitals in Egypt (Aldemrdash hospital representing Ain Shams University and Qena public hospital) in a group of Egyptian pediatricians (n=150) to determine the three most commonly prescribed antibiotics there. The three antibiotics were Duricef, E-moxclav and Suprax. Artificial saliva was also used in this study as a control. Second, pH and titratable acidity of the all used solutions were measured. Class I cavity was prepared for all teeth then they were restored with self adhesive glass ionomer restoration (Equia ™Fil). Teeth were thermcylcled then they were randomly divided into four groups for drug immersion for 14 days with daily change of the solution. Teeth then were prepared for staining with methyle blue dye. Results: According to scoring criteria of Khera and Chanas , Score 1 was for Duricef and E-moxclav groups while score 2 was for Suprax group. Score 0 was for control group. Conclusion: Antibiotics commonly used for children had negative effect on marginal adaptation of glass ionomer restoration.