Objectives: This study compared medical treatment costs of adults with schizophrenia to adults with both substance use disorders and schizophrenia. Methods: This cross-sectional observational study used a paid claims data base to identify 6884 adults treated for schizophrenia. Twenty percent of these also had substance use disorder. We report the costs and likelihood of hospitalization for eight common medical diseases, and the categories of injuries and poisoning, and ill defined conditions. Multivariate analyses were used to adjust rates of treatment for age and sex differences in the comparison groups. Results: There were higher rates of treatment for five of the eight medical disorders, higher treatment costs for two of the medical disorders and much higher costs for psychiatric treatment among those with comorbid substance use disorders. Both groups had high rates of treatment in the categories of injury and poisoning and ill defined conditions. Conclusions: Closer working relationships among mental health and medical professionals are needed to care for those with schizophrenia and substance use disorders: first, greater attention to the treatment of substance use disorders may improve the health status of those with schizophrenia, reduce their costly medical and psychiatric care and stabilize their psychiatric condition, and second, continuity of care among professionals may promote willingness to seek medical attention or alleviate misunderstandings when adults with schizophrenia present with medical problems.