Objective: The purpose of this study was to investigate whether the presence of substance-related disorders or mental illness may affect the quality of medication management in asthma care. Methods: Claims from 1999 for adult Medicaid patients with persistent asthma from five states were analyzed. Sample sizes ranged from 1,207 to 5,815. The adjusted odds of meeting two quality-of-care measures for asthma were calculated: the Health Effectiveness Data and Information Set (HEDIS) measure of filling a single prescription for a controller medication and a non-HEDIS measure of achieving a ratio of long-term controller medications to total asthma medications of >=.5. Results: Odds of achieving the HEDIS measure were lower for patients with substance-related or schizophrenia disorders in two states (range of odds ratio [OR]=.69, 95% confidence interval [CI]=.53-.90, to OR=.81, 95% CI=.69-.96), but the odds increased for patients with depressive disorders in two states (OR=1.34, CI=1.12-1.61; OR=1.37, CI=1.05-1.77) and for patients with bipolar disorder in one state (OR=1.69, CI=1.13-2.55). Odds of achieving the ratio measure were lower for patients with substance-related disorders in four states (range of OR=.63, CI=.47-.88, to OR=.75, CI=.62-.92) and higher for patients with depressive disorders, although only in one state (OR=1.25, CI=1.03-1.53). Conclusions: Patients with substance-related disorders and those with schizophrenia disorders may be receiving lower-quality asthma care, whereas patients with some other forms of mental illness may be receiving higher-quality care. Further studies are needed to identify the determinants of high-quality asthma care and the validity of quality measures based on administrative data in these populations. (Psychiatric Services 60: 43-49, 2009)