Objectives: The present study aimed to investigate risk and protective factors of drug abuse among high school students. Method: The sum of 1124 high school students (573 boys and 551 girls) were selected based on the stratified random and cluster sampling from Tehran’s high schools. A number of different scales American Drug and Alcohol Survey (ADAS), Prevention Planning Survey (PPS), Blings-Moss Copying Responses (CR), Cooper-Smith Self-Esteem Inventory School Form (SEI-SF), Collins-Reed Revised Attachment Inventory (RAI), and Bar-On Emotional Quotient Inventory (EQI) were administered for data gathering. The data were analyzed using t-test, chi-square, logistic regression and odds ratio models. Results: There were significant differences between students with and without drug abuse in copying styles, self-esteem, attachment style, emotional intelligence, family atmosphere and family substance abuse. Odds ratio of drug abuse for students with family drug use for boys and girls was 11 and 1.63 times more than others respectively. Conclusion: In the recent years, the most important achievement in the areas of theorizing and policy-making for drug abuse preventive programs is to emphasis on risk and protective factors as a descriptive and predictive framework. This study findings emphasized family factors, self-esteem, emotional intelligence and coping styles in this regard