INTRODUCTION:Children are frequently subjected to liquid medications, especially antibiotics. They are acidic, have low pH and high titratable acidity. This can erode enamel. AIM: This in vitro study aim to determine the correlation between antibiotics as regards their erosive effect and frequency of intake on primary enamel integrity. MATERIALS AND METHODS: Three commonly prescribed pediatric antibiotics groups: macrolides, cephalosporins and mixed composition were chosen. pH and titratable acidity of the selected antibiotics and artificial saliva were determined. Seventy seven human primary teeth, exfoliated or extracted for orthodontic reasons were randomly assigned to three antibiotics groups and a control group, 11specimens for each group. Specimens were immersed in fresh solutions of antibiotics for 1 minute over 3, 5and 10 days, depending on the type of antibiotic. All samples were preserved in artificial saliva in between immersion cycles. Enamel micro hardness was evaluated at baseline, 3& 5&10 days. RESULTS: Highest percent reduction was recorded for the mixed antibiotic (24.39 ±4.65) P<0.0001, followed by cephalosporin (13 . 79 ±4.37) P<0.0001 and macrolides (7.99 ±2.82) P<0.0001. Mixed type immersed for 10 days showed the highest reduction in microhardness (37.00 ±4.71). Macrolides for 3 days showed the lowest reduction (12.22 ±3.20). All the experimental groups recorded loss in microhardness with high significant difference P<0.0001. CONCLUSION: Tested antibiotics could erode enamel even when pH is above critical and low titratable acidity. Increasing duration and frequency of prescription, increases the erosive potential.