AIMS To determine levels of systemic disease among cases of death due to opioid toxicity. DESIGN Analysis of coronial cases. SETTING Sydney, Australia. CASES A total of 841 cases of death due to opioid toxicity (1 January 1998-31 December 2002). FINDINGS Ventricular hypertrophy was present in 5.9% of cases and severe coronary artery atherosclerosis in 5.7%. Severe coronary pathology was more pronounced among older cases. Pre-existing bronchopneumonia was present in 13.2% of cases. Hepatic pathology was the most common type of pathology, and was far more marked among older cases. Cirrhosis was present in 25.3% of those aged > 44 years. Levels of renal pathology were comparatively low, but were related significantly to increasing age. Systemic disease in more than one organ system was present in 24.4% of cases, and was related to increasing age (44% of those aged > 44 years). The only pathology for which gender was an independent predictor among opioid cases was ventricular hypertrophy, more common in males. CONCLUSIONS Systemic disease, most prominently liver disease, is common among fatal opioid toxicity cases, and may be a factor in understanding the dynamics and age demographics of opioid-related death.