Background: The direct and indirect effects of substance of abuse on children lead to many adverse health and safety risks for the child, family and community. Patterns of drug abuse in children are determined not only by the availability and cost of different substances, but also by the dynamics and differences within groups, cultures and age groups. There is increasing awareness that the abuse of drugs by parents and other caregivers can have a good impact on the safety, permanence and well-being of children. Objective: The purpose of this study was to shed light on the prevalence of drug of abuse in children in toxicology unit in Damietta governorate from the 1st of May 2015 to 1st of January 2017. Subjects and Methods: A total of 100 abused child were detected to estimate the prevalence of drug abuse in children in Toxicology unit Al-Azhar University Hospital (New Damietta) from the 1st of May 2015 to 1st of  January 2017, in addition to 20 healthy volunteers as a control group. Within one hour after arrival to emergency room, blood samples were drawn in sodium fluoride (NaF) contained tubes. Then, it was kept at 4-8 ^oC for subsequent test, using radioimmunoassay strips as a preliminary test, and a high performance liquid chromatography (HPLC) as a confirmatory test. The status of electrolytes, hemoglobin (Hb), liver and renal function tests, and alkaline phosphatase level were evaluated at the same time of screening the substance abuse. Cases and controls were subjected to full medical history with stressing on age, sex, smoking, behaviors, difficult temperament and the psychoactive drugs used during the previous month. This was in addition to  clinical examination with special attention to neurological examination and Glasgow Coma Scale (GCS). Results: The most common drugs abuse in children were tramadol (90.0%) followed by both cannabis and drugs- co-administration (50.0%), anti-psychotic drugs (30.0%), benzodiazepines (26.0%), antihistamines (13.0%), amphetamine (10.0%), then antidepressants and cough suppressants (5.0%). In control group, tramadol was also the most common drugs abuse (35.0%) followed by cough suppressants (30.0%), cannabis (25.0%), anti-psychotic drugs, benzodiazepines and drugs- co-administration (20.0% for each one), then followed by antihistamines and antidepressants (10.0% for each one). There was a significant difference in tramadol, cannabis, cough suppressants, and drugs-co administration in the study group in comparison to control group. Conclusion: Tramadol is the most common drug abuse in children in Toxicology Unit in Damietta Governorate, followed by both cannabis and drugs- co-administration, anti-psychotic drugs benzodiazepines, antihistamines, amphetamine, then both antidepressants and cough suppressants respectively.