Substance use and risk-taking behavior among 1,227 Israeli youth (66.7% male, 33.3% female) were studied from 2004 to 2016. The youth compared included those who: 1) attended regular public school; 2) were placed in residential programs for learning and/or behavior problems; and 3) were school dropouts referred to a 90 day treatment facility for drug abuse. Country of origin, determined by mother`s birthplace, revealed 42.6% of the youth was of Israeli origin and 57.4% from other countries – mostly the former Soviet Union and Ethiopia. The data collection instrument used, the Substance Use Survey Instrument (SUSI), was developed by the Ben Gurion University Regional Alcohol and Drug Abuse Research Center in consultation with experts affiliated with the US National Institute on Drug Abuse and the World Health Organization. SUSI consists of 31 questions about background characteristics, substance use patterns and related problem behavior. Chi square test, one-way ANOVA, and binary logistic regression were used to determine association between substance use, problem behavior and country of origin status. Results showed that immigrant origin youth, regardless of country of origin, have similar patterns of substance use and risk-taking behavior; and, they have higher levels of substance use and problem behavior (e.g. binge drinking, marijuana use, serious fighting, and stealing) than Israeli origin youth. Such results tend to indicate that substance use as well as problem behavior among immigrant origin youth may be a result of inadequate acculturation and marginalized status. Further research is suggested for different immigrant populations across locations and over time.