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Poisoning is a significant public health threat as the second leading cause of injury-related death in the US. Disagreements on cause of death determination may have widespread implications across several realms of public health including policy and prevention efforts, interpretation of the poisoning literature, epidemiologic data analysis, medical-legal case outcomes, and individualized autopsy interpretation. We aimed to test agreement between the cause of death determined by the medical examiner (ME) and a medical toxicologist (MT) adjudication panel (MTAP) in cases of poisoning. This retrospective 7-year study evaluated all deaths attributed to poisoning in one large urban catchment area. Cross-matched data were obtained from Department of Vital Statistics and the Poison Control Center (PCC). Out of >380,000 deaths in the catchment area over the study period, there were 7050 poisonings in the Vital Statistics database and 414 deaths reported to PCC. Cross-matching yielded 321 cases for analysis. The ME and MTAP concurred on cause of death in 66%, which was only fair agreement (κ 0.25, CI 0.14–0.38). Factors associated with the likelihood of agreement were peri-mortem fire exposures, prehospital cardiac arrest, and timing of drug toxicity (chronic versus acute). In conclusion, agreement for poisoning cause of death between specialties was much lower than expected. We recommend an improved formal process of information sharing and consultation between specialties to assure that all existing information is analyzed thoroughly to enhance cause of death certainty.