Aims-To evaluate, among intravenous drug users (IDUs), the hypothesized positive association of depression with substance-related behaviors including concurrent drug use and impairment, future drug use and impairment, alcohol use and impairment, needle sharing and substance use treatment participation, and to identify moderators of these associations.Design-Meta-analysis of reports on IDUs published in English in peer-reviewed journals since 1986 that contained data on depression and substance use outcome(s) with no restrictions on range of depression scores to select the sample.Setting-Fifty-five reports containing 55 samples met criteria, including 42 (76%) samples from clinical venues and 13 (24%) that were community-based.Participants-Mean age was 34.3 (standard deviation = 4.5) years, comprising approximately 68% men and 43% white, non-Hispanic subjects.Measurements-Depression was assessed with the Beck Depression Inventory, Center for Epidemiological Studies Depression Scale (CES-D) and other validated scales or diagnostic interviews. The Addiction Severity Index was the most frequently used measure of substancerelated outcomes.Findings-A priori hypotheses pertaining to depression and the substance-related variables were supported, with the exception of the predicted association of depression and future drug use and impairment. Effect sizes were small. Moderating effects of gender were identified, including greater associations of depression with substance use treatment participation and needle sharing among women and a greater association of depression with future drug use and impairment among men. Effect sizes of moderators were large.Conclusions-Depression is associated with several substance-related behaviors, and select associations are stronger according to gender. Prospective associations of depression with future drug use and impairment are not immediately evident, but could be examined in subsequent research.