Key PointsQuestionWhat has been the association between relaxing restrictions on take-home methadone doses and the number of fatal overdoses involving methadone among different racial, ethnic, and sex groups?FindingsIn this interrupted time series cohort study of 14 529 methadone-involved overdose deaths, the methadone take-home policy was associated with reduced deaths among Black and Hispanic men but did not affect deaths of Black or Hispanic women or White men or women.MeaningThe urgency of the overdose crisis requires that national methadone policy debates and decisions address the heterogeneity of people in treatment; relaxing methadone restrictions may help some particularly at-risk groups.