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Background: Substance abuse is associated with injuries, but these associations have not been well characterized by type of substance and injury type., Methods: A cross-sectional study of patients selected for toxicology screening compared those with positive and those with negative test results for drugs and alcohol., Results: Patients with positive alcohol toxicology results were more likely to have violence-related and penetrating injuries than patients with negative results. However, after adjustment for positive cocaine toxicology results, the association between alcohol and penetrating injury was no longer significant. Positive test results for any drug were not associated with any specific injury type, but cocaine was independently associated with violence-related injury. The associations of alcohol and cocaine with violence-related injury appear to be additive. In contrast, opiates were independently associated with nonviolent injuries and burns., Conclusions: Alcohol and cocaine use is independently associated with violence-related injuries, whereas opiate use is independently associated with nonviolent injuries and burns.