The abuse of opioids is a serious and prevalent problem and research is needed on factors that may place individuals at risk for misusing opioids. Depression is a common co‐morbid mental health problem among opioid users. Theory and research suggest that early maladaptive schemas may underlie mental health problems including depression and substance abuse. The current study sought to determine whether early maladaptive schemas were associated with depression among a treatment seeking sample of male and female opioid users (n = 194). We also examined whether depression, as assessed by the Minnesota Multiphasic Personality Inventory, Second Edition, varied by gender and whether gender differences in depression remained after controlling for early maladaptive schemas. Results showed that women scored significantly higher than men on three of the five early maladaptive schema domains and that gender did not predict depression after controlling for schema domains. Early maladaptive schemas were also more strongly associated with depression for men than women. Implications of these findings for interventions and future research are discussed. Copyright © 2012 John Wiley & Sons, Ltd. Key Practicioner Message Individuals with opioid dependence have a number of early maladaptive schemas that may be contributing to the onset and maintenance of substance use. Although there are generally broad gender differences in major depression, findings from the current study suggest that early maladaptive schemas are a better predictor of depressive symptoms than gender among opioid dependent adults. The treatment of opioid dependence, with or without co‐morbid depressive symptoms, should target early maladaptive schemas.