Background: Drug addiction is a major public health and socioeconomic problem worldwide that annoys the Egyptian government, as it deals with youth within the age of productivity. Aim of the Work: To determine the prevalence of drug abuse among Zagazig University students. Subjects and Methods: A cross-sectional study conducted on 750 students in Zagazig University from the beginning of November 2015 to the end of November 2016, after an informed verbal consent. Data were collected through a self-administrated questionnaire and the results of screening urine samples. Results: The prevalence of drug abuse in general was 7.41%. The prevalence of drug abuse in descending order was tetrahydrocannabinol (3.9%) followed by tramadol (1.9%) then benzodiazepines (0.67%), while, opium and barbiturates each one of them (0.47%). 18% of them were Polydrug users and were only males. Tramadol was the commonest drug to use in polydrug users. The prevalence of smoking was 16.81% and strongly related to gender as in males 26.1% were current smokers while in females only 1.4%. The prevalence of abusing alcohols was 6%, and all of them were males. Conclusion: The prevalence of drug abuse in Zagazig university students is considered high and a very serious problem damaging the youth and the community. Recommendation: Future longitudinal studies should be conducted to investigate the risk factors of drug abuse and suggest the use of urine analysis for drugs of abuse for all students before joining the university.