Objective: The aim of this study was to determine the prevalence of substance use and addiction in Egypt and study its sociodemographic correlates. Method: A total of 44,000 subjects were interviewed from 8 governorates by stratified sampling. A questionnaire derived from the Addiction Severity Index (ASI) was individually administered. Results: The lifetime prevalence of any substance use varies between 7.25% and 14.5%. One-month prevalence varies between 5.4% and 11.5% when adjusted to different population parameters. A total of 4832 subjects were identified as using illicit substances at least once in their life (9.6%), including 1329 experimental and social use (3.3%), 1860 regular use (4.64%), and 629 substance dependence (1.6%). The prevalence of substance use in males is 13.2% and 1.1% in females. Prevalence increases significantly in males of Bedouin origin, in seaside governorates, with lesser levels of education, and in certain occupations. The 15–19 age group showed the highest onset of substance use. Cannabis is the drug mostly misused in Egypt; alcohol is a distant second. Conclusions: The prevalence of substance use is lower than Western countries and higher compared with a 1996 survey. The true population prevalence is probably higher due to underreporting. The demographic pattern reflects availability and accessibility to drugs.