The relation between illicit drug dependence and the likelihood of drug overdose is unclear. We recruited 1,066 habitual drug users for this analysis through street-based outreach in New York City. In this sample, 99.3% of respondents used heroin in the past year and 87.1% of respondents used cocaine; 819 (77.5%) heroin users and 735 (79.2%) cocaine users were severely dependent on either drug respectively. In multivariable models, among heroin users, persons who were severely heroin dependent were less likely (OR = 0.6; 95% CI = 0.4-0.9) to have overdosed on any drug in the past year; among cocaine users, those who were severely cocaine dependent were more likely (OR = 1.6; 95% CI = 1.0-2.6) to have overdosed in the past year. The relation between illicit drug dependence and risk of overdose may vary for different patterns of drug dependence. These observations suggest that overdose prevention interventions, perhaps even those specifically targeting opiate overdose, may be more efficiently directed at individuals exhibiting cocaine dependence.