Substance misuse is usually associated with poorer psychiatric medication adherence among psychiatric patients. Identifying predictors of medication adherence among patients with dual psychiatric and substance misuse problems is important because poor adherence is associated with relapse and re-hospitalization. The subjects were patients newly admitted to a psychiatric outpatient program who were prescribed psychiatric medication from different providers during the six months prior to admission; all also had substance misuse histories (N=131). Confidential research interviews were conducted that included a modified Medication Adherence Rating Scale (MARS) and drug toxicologies. Age (mean): 39 y; male 61%; Black 41%; Hispanic 38%; White 21%; completed high school/GED 41%; DSM-IV diagnoses: major depression 26%, schizoaffective 21%, bipolar 16%, schizophrenia 13%, other 24%; positive drug toxiology 55%. Potentially malleable factors correlated with lower adherence were: lower friends' support for drug/alcohol abstinence, more recovery-promoting behaviors, lower satisfaction with medication, more medication side effects, lower self-efficacy for drug avoidance, and lower social support for recovery. In multivariate regression analysis, only the last three factors remained as significant predictors of adherence. Low adherence is not attributable to simply forgetting to take medication. Strengthening adherence should also include better education about side effects and the importance of adherence to sustain the benefits of medication. Psychiatrists and other medical providers should also be encouraged to address patients' adherence strategies, since the time devoted to addressing that during treatment may prevent serious adverse events such as relapse to substance abuse, treatment drop-out and re-hospitalization.