Little is known about risk factors for depression in methamphetamine users. Using data from 526 adults in the largest psychosocial clinical trial of methamphetamine users conducted to date, this study examined clinical, demographic, and substance use characteristics that predict the presence of a diagnosis of major depressive disorder (MDD) three years after treatment for methamphetamine dependence. The results indicate that two risk factors predict a diagnosis of MDD: a Beck Depression Inventory total score greater than 20, and one or more prior suicide attempts. These risk factors identify methamphetamine users who may benefit from early interventions for psychiatric symptoms.