Over the past 2 decades, neonatologists have cared for growing numbers of infants who were exposed passively in utero to a variety of licit and illicit drugs consumed by their mothers. Applying specific written guidelines to select newborns for drug testing decreases bias and protects the physicians and hospitals involved. Meconium (MEC) and umbilical cord blood (UCB) are a biological markers of in utero exposure to illicit drugs. So, the purpose of this study was used to detect the exposure of the infant to drug of abuse in MEC and UCB in obstetric units in Al-Azhar University Hospital (New Damietta) from the 1st of may 2014 to 1st of April 2016. for close follow-up of the infant by both medical and social services. It involved 100 infant from a delivery women's in obstetric room in Al-Azhar University Hospital (New Damietta) with history of smoke inhalation by the mother, history of drug of abuse in present or previous pregnancies, maternal report of drug abuse during this pregnancy, demonstration of drug in maternal urine, limited prenatal care (<5 prenatal visits), history of hepatitis C, B, AIDS, syphilis, gonorrhea, unexplained placental abruption and unexplained premature labor or Infants who have any of the following unexplained neurologic complications (e.g., intracranial hemorrhage or infarction, seizures), evidence of possible drug withdrawal (e.g., hypertonia, irritability, seizures, tremulousness, muscle rigidity, decreased or increased stooling) and unexplained intrauterine growth retardation and 50 infant of normal labour without any history of maternal drug abuse or fetal complication as a control group. After free informed consent to participate in this study, all the studied infants were submitted to the following:- full medical history, clinical examination. After delivery, 3 grams of MEC and 10 ml of UCB were collected and extracted for toxic metabolites. Immunoassays as a preliminary test then high performance liquid chromatography (HPLC) were used. Positive drug of abuse metabolites from UCB in the studied groups were, cough suppressant was positive in (50.0%), cannabinoid was positive in (80.0%), morphine was positive in (60.0%), tramadol was positive in (70.0%), methadone was positive in (90.0%), cocaine was positive in (10.0%), diazepam was positive in (56.0%) and amphetamine was positive in (6.0%). Drug of abuse metabolites from MEC in the studied groups were, cough suppressant (codeine) was positive in (40.0%), cannabinoid, morphine and tramadol were positive in (50.0%), methadone and amphetamine were positive in (10.0%) and diazepam was positive in (55.0%). In conclusion; MEC and UCB were considered as a useful tool to detect the maternal drug abuse, there is a high agreement between results of UCB and MEC testing. It is recommended that; Identification of drug-of abuse in mothers before or early in pregnancy would be ideal and avoiding intrauterine exposure, the benefits of identifying of drug-of abuse in mothers and her infants could include; programs for improvement of parenting skills with sharing of television, radio and social media, maternal drug treatment, home assistance, focused medical observation during the newborn period, restriction of breast-feeding, close pediatric follow-up emphasizing developmental and social issues and early discovery of maternal with drug-of abuse and successful maternal treatment, leading to decreased postnatal infant exposure, which can have deleterious effects and decreased risk of drug-of abuse in future pregnancies.