Objective: There is an increase in persons entering substance use treatment who co-use opioids and methamphetamines in recent years. Co-using these substances may negatively impact treatment retention in the residential setting. We explored predictors of adults completing short-term residential treatment among persons with primary opioid use disorder (OUD) who co-use either alcohol, benzodiazepines, cocaine, or methamphetamines.Methods: This study used the 2019 de-identified, publicly available Treatment Episode Dataset-Discharges. The sample included adults discharged from short-term residential treatment with primary OUD who co-used either alcohol, benzodiazepines, cocaine, or methamphetamines. The final sample size included 24,120 treatment episodes. Univariate statistics were used to describe the sample. Two logistic regression models were used to predict completing treatment. The first logistic regression model included the co-use groups as predictors and the second model added other demographic and treatment-relevant covariates.Results: A slight majority (51.4%) of the sample prematurely discharged from treatment. Compared to the other three co-use groups, the opioid and methamphetamine co-use group had the highest proportion of individuals who were women (45.0%), unemployed (62.5%), current injection drug use (76.0%), living in the Midwest (35.9%), living in the south (33.5%), and living in the west (15.5%). The opioid and methamphetamine co-use group also had the highest proportion of individuals not receiving medications for OUD (84.9%), not having a prior treatment episode (28.7%), and not completing treatment (57.4%). In the final logistic regression model, which included covariates, the opioid and alcohol (OR = 1.18, 95% CI = 1.080–1.287, p < 0.001), opioid and benzodiazepine (OR = 1.33, 95% CI = 1.213–1.455, p < 0.001), and opioid and cocaine (OR = 1.16, 95% CI = 1.075–1.240, p < 0.001) co-use groups had higher odds of completing treatment than the opioid and methamphetamine co-use group.Conclusions: Opioid and methamphetamine co-use may complicate short-term residential treatment retention. Future work should identify effective strategies to retain persons who co-use opioids and methamphetamines in treatment.