Despite the knowledge that residential substance abuse treatment completion is effective in improving outcomes among chronic substance users, a large proportion of African American residential treatment-seeking substance users experience premature treatment dropout. Previous studies have examined the predictors of early substance abuse treatment dropout; however, a deeper understanding of the conditions that influence treatment dropout among urban African American substance users is limited. Taking the perspectives of the Theory of Planned Behavior, the Stages of Change Model, and the Negative Reinforcement Model, this study examined (1) the interacting effect of intention to complete treatment and distress tolerance on treatment dropout, and (2) the interacting effect of motivation to change substance use behavior and distress tolerance on treatment dropout in a sample of urban African American treatment-seeking substance users. Data were collected from 81 African American substance users entering residential substance abuse treatment facility in an urban setting. Participants completed measures assessing intention to complete treatment, motivation to change substance use behavior, and distress tolerance, as well as measures assessing psychiatric comorbidities, impulsivity, previous treatment, treatment barriers, court-mandated treatment, and demographic information. Participants also engaged in a behavioral measure of distress tolerance. Treatment dropout data were obtained using administrative records of the treatment center. Results from logistic regression analyses indicated that only the interaction between motivation and self-reported distress tolerance was significant in predicting the likelihood of treatment dropout after controlling for relevant covariates, including employment, psychiatric comorbidities, and court-mandated treatment status. Probing of this interaction effect showed that higher motivation was significantly associated with decreased likelihood of treatment dropout among substance users with higher distress tolerance, but not in substance users with lower distress tolerance. Findings of the study suggest that higher motivation and higher distress tolerance may be both necessary for reducing the risk of treatment dropout among urban African American treatment-seeking substance users. Interventions to decrease treatment dropout among substance users may benefit by incorporating motivational strategies, such as motivation interviewing, and distress tolerance skills into their programs to reduce treatment dropout.