This randomized study examined the efficacy of motivational interviewing (MI) to reduce substance use among adults with depression in outpatient psychiatry. The sample consisted of 104 participants ages 18 and over who reported hazardous drinking (three drinks or more per occasion), illegal drug use or misuse of prescription drugs in the prior 30 days, and who scored >/= 15 on the Beck Depression Inventory-II (BDI-II). Participants were randomized to receive either three sessions of MI or printed literature about alcohol and drug use risks, as an adjunct to usual outpatient depression care, and completed telephone follow-up interviews at 3 and 6 months (93 and 99% of the baseline sample, respectively). Among participants reporting any hazardous drinking at baseline (n=73), MI-treated participants were less likely than controls to report hazardous drinking at 3 months (60.0 vs. 81.8%, p=.043). MI is a promising intervention to reduce hazardous drinking among depression patients.