BACKGROUND AND OBJECTIVES:Prevailing literature explains how depression, compulsion, and mindfulness affect heroin use; however, there is no comprehensive framework that explains their overall relationships. We therefore proposed and examined a hypothetical depression-compulsion-heroin use and mindfulness (DCHm) model. METHODS: We recruited 234 male heroin users. Self-reported levels of depression, mindfulness, compulsion to use, and severity of heroin use were measured. Structural equation modeling was used to examine the proposed DCHm model. RESULTS: Compulsion was a mediator between depression and heroin use. In addition, the DCHm model had satisfactory model fit indices. Depression indirectly affected heroin use through compulsion to use. The moderating effects of mindfulness in the two competing models were compared between the high- and low-mindfulness groups. The DCHm model in the high-mindfulness group had more favorable model fit indices than it did in the low-mindfulness group. CONCLUSIONS: Through learned emotional regulation strategies, addicted people with higher mindfulness were less likely to compulsively take drugs because of a depressive mood than were those with lower mindfulness. Furthermore, effective emotion-regulation strategies should be developed and examined in future studies. SCIENTIFIC SIGNIFICANCE: These results raise questions about the effect of compulsion on heroin use disorders. Mindfulness-based approaches to emotional regulatory strategies should be developed based on these findings. Further experimentation and prospective studies are needed to more fully examine the moderating role of mindfulness on depression and compulsion.