This study characterizes the prevalence of drug use among Filipino street children compared with Filipino non-street children. A cross-sectional survey was administered to 311 street children and 528 non-street children aged 13 to 17 years. Participants were enrolled through 4 nonprofit organizations and 3 high schools located in Manila, Philippines. After adjustment for age and sex, street children with little or no contact with their families were 2.0 (95% confidence interval [CI] = 1.7-2.3) times more likely to smoke tobacco, 1.3 (95% CI = 1.2-1.5) times more likely to use alcohol, 36.7 (95% CI = 16.4-82.0) times more likely to use inhalants, and 5.5 (95% CI = 3.6-8.2) times more likely to use illegal drugs than their non-street counterparts. Street children who maintained contact with their families, compared with non-street children, were 8.7 (95% CI = 3.9-19.4) times more likely to use inhalants and 2.8 (95% CI = 1.7-4.6) times more likely to use illegal drugs. There was no significant difference in tobacco or alcohol use between street children who maintained contact with their families and non-street children. All street children were significantly more likely to have been given or sold a drug in the past 30 days and to have received drug education compared with non-street children. Filipino street children are at greater risk of abusing drugs than are non-street children, with street children who do not maintain family contact being at greatest risk.