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Studies have established that comorbidity needs to be considered when assessing and treating substance-using clients. This study explores course of treatment, risk factors, and drug-related issues among 192 ethnically diverse pregnant women who were actively using drugs at admission to a residential treatment program. Findings revealed that course of treatment is more difficult for comorbid clients who perceived more treatment barriers than noncomorbid clients. Comorbid clients were more likely to have a history of attempting suicide but no more likely to have been reported for child abuse or charged with a crime. Comorbid clients reported greater severity of alcohol use but did not differ from noncomorbid clients regarding drug of choice. Comorbid clients were no more likely to leave against treatment advice, and noncomorbid clients were no more likely to complete treatment. Findings suggest that sensitivity to comorbidity issues is crucial to retaining comorbid clients in treatment.