Abstract: This study, the largest randomized controlled trial of treatment for major depressive disorder (MDD) in an incarcerated population to date, wave-randomized 38 incarcerated women (6 waves) with MDD who were attending prison substance use treatment to adjunctive group interpersonal psychotherapy (IPT) for MDD or to an attention-matched control condition. Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants. Control participants improved later, after prison release. IPT’s rapid effect on MDD within prison may reduce serious in-prison consequences of MDD.