Failure in medication compliance in adult psychiatric patients is often found to be due to side effects or associated with unawareness of illness. Little research has been conducted on medication compliance in adolescent psychiatric patients. In this study, 97 adolescent psychiatric patients, including 46 with substance abuse, were followed up an average of 14 months after their discharge from inpatient psychiatric care. Compliance with prescribed medications was examined and the association between several potential predictors and compliance was examined. The overall rate of medication compliance was only 38% at 14-month follow-up, whereas the rate of patients stopping their medications because of side effects was only 23%. Significant predictors of compliance failures were general noncompliance with the discharge plan, followed by postdischarge substance abuse. Side effects did not contribute any additional variance when these factors were considered. These data suggest that medication compliance may be adversely impacted by general tendencies toward noncompliance with treatment, which may be mediated by several possible factors. Interventions to increase awareness of the need for psychotropic medications as well as careful monitoring for substance abuse relapse in this population are suggested.