Objective: Comorbidity and co-prescription patterns of people with serious mental illness in methadone maintenance may complicate their treatment and have not been studied. The goal of this study was to examine the care and characteristics of people with serious mental illness in methadone maintenance treatment nationally in the Veterans Health Administration (VHA). Methods: Using national VHA data from FY2012, bivariate and multiple logistic regression analyses were used to compare veterans in methadone maintenance treatment wo had a serious mental illness (schizophrenia, bipolar disorder, or major affective disorder) to patients in methadone maintenance treatment without serious mental illness and patients with serious mental illness who were not in methadone maintenance treatment. Results: Only a small fraction of patients with serious mental illness were receiving methadone maintenance treatment (0.65%), but a relatively large proportion in methadone maintenance treatment had a serious mental illness (33.2%). Compared to patients without serious mental illness, patients with serious mental illness in methadone maintenance treatment were more likely to have been homeless, to have had a recent psychiatric hospitalization, to be over 50% disabled, and to have had more fills for more classes of psychotropic drugs. Compared to other patients with serious mental illness, patients with serious mental illness in methadone maintenance treatment were more likely to have a drug abuse diagnosis and to reside in large urban areas. Conclusions: One-third of patients in methadone maintenance treatment have serious mental illness and more frequent psychiatric comorbidity, and they are more likely to use psychiatric and general health services and fill more types of psychiatric prescriptions. Further study and clinical awareness of potential drug-drug interactions in this high medication and service using population are needed.