Background: The difficulties in engaging and treating individuals with comorbid psychiatric problems and substance misuse has been acknowledged as a growing problem likely to have implications for treatment. Aims: This study compared service use in clients with single and comorbid diagnoses from Adult Mental Health (AMH) and Drug and Alcohol services (DAS). Methods: A retrospective matched case-control study of a sample of service users of a mental health Trust in East Anglia drawn across AMH (n = 400) and DAS (n = 190). Odds ratios were estimated and used to test for differences in client groups with respect to uptake of community services, formal and informal in-patient services, "out-of-hours" services and engagement with statutory services. Results: Marked differences were observed in terms of service use between clients of AMH who had a single diagnosis of severe, chronic or recurrent psychiatric problems and clients of AMH who had additional substance misuse problems. Differences were less pronounced between clients of DAS who had a single diagnosis of substance misuse and clients of DAS who had substance misuse and psychiatric problems. Conclusions: Different patterns of service uptake were observed between singly diagnosed and comorbid AMH clients. There was a lack of differences in patterns of service uptake in singly diagnosed and comorbid DAS clients. Substance misuse could be a factor influencing service uptake rather than comorbidity per se.