AIMS: To estimate risk of death due to cardiac arrhythmia during methadone maintenance treatment. BACKGROUND: There is evidence that methadone prolongs the QT interval, and has been associated with ventricular tachycardia in some individuals. METHODS: We identified 51 deaths occurring during methadone treatment, occurring in a cohort with a defined exposure to methadone treatment. We obtained consent to access coronial records to investigate these in-treatment deaths in detail, to identify potential cases of fatal arrhythmia--those cases in which sudden death occurred without clear evidence of an alternate cause of death. We obtained consent to access clinic records of dosing. Two physicians reviewed the coronial files and circumstances of death. The total number of person-years exposure to methadone treatment was calculated. RESULTS: There were extensive missing data in coronial and clinic files, making definitive assessment difficult in many cases. No definite case of death due to cardiac arrhythmia was identified. There were two cases in which arrhythmia seemed possible, and 10 cases in which arrhythmia could not be excluded. The study covered 14,500 patient-years (pys) in methadone treatment, yielding an estimate from 0 to 0.069 deaths per 100 pys, with a best estimate of fatal arrhythmia occurring at a rate of 0.014 per 100 pys. Overdose is a more common cause of death. Both potential arrhythmias and overdoses were associated with use of other drugs in addition to methadone—usually, prescription drugs or methamphetamine. CONCLUSIONS: The risk of fatal cardiac arrhythmia in methadone maintenance patients appears to be low. The major risk factor for death was use of prescription drugs, and methamphetamine, in addition to methadone.