This study was undertaken to compare cocaine-dependent patients with and without an opioid use disorder, in an effort to identify important clinical similarities and differences between the two groups. Ninety patients hospitalized for cocaine dependence were divided according to whether or not they had a coexisting opioid use disorder; 32 patients (35.6%) had an opioid diagnosis and 58 (64.4%) did not. The groups were compared on substance use histories, psychopathology, severity of drug-related problems, and 3-month cocaine use outcome. Patients with an opioid diagnosis had more current major depression, antisocial personality disorder, and other substance use disorders. They also had higher medical and drug scores on the Addiction Severity Index, and longer cocaine use histories. Nonetheless, 3-month cocaine use outcome was similar for both groups. Interestingly, patients with an opioid diagnosis engaged in more treatment during the follow-up period. Cocaine-dependent patients with a coexisting opioid use disorder may thus constitute a subgroup with worse prognostic characteristics, for whom differential treatments may improve outcome.