Description: An expert panel convened by the Center for Substance Abuse Treatment developed safety recommendations for physicians prescribing methadone. Methods: Expert panel members reviewed and discussed the following data regarding methadone: pertinent English-language literature identified from MEDLINE and EMBASE searches (1966 to June 2008), national substance abuse guidelines from the United States and other countries, information from regulatory authorities, and physician awareness of adverse cardiac effects. Recommendation 1 (Disclosure): The panel recommends that clinicians inform patients of arrhythmia risk when they prescribe methadone. Recommendation 2 (Clinical History): The panel recommends that clinicians ask patients about any history of structural heart disease, arrhythmia, and syncope. Recommendation 3 (Screening): The panel recommends obtaining a pretreatment electrocardiogram for all patients to measure the QTc interval and a follow-up electrocardiogram within 30 days and annually. The panel recommends additional electrocardiography if the methadone dosage exceeds 100 mg/d or if patients have unexplained syncope or seizures. Recommendation 4 (Risk Stratification): If the QTc interval is greater than 450 ms but less than 500 ms, discuss the potential risks and benefits with patients and monitor them more frequently. If the QTc interval exceeds 500 ms, the panel recommends considering discontinuation or reduction of the methadone dose; elimination of contributing factors, such as drugs that promote hypokalemia; or use of an alternative therapy. Recommendation 5 (Drug Interactions): The panel recommends that clinicians be aware of interactions between methadone and other drugs that possess QT interval-prolonging properties or slow the elimination of methadone.