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Background: Recent overdose trends are characterized by increased toxicological detection of stimulants with opioids, yet it is unclear whether these substances are mixed prior to consumption or purposefully used simultaneously.Methods: Postmortem toxicology data were collected in Marion County, Indiana, from 45 fatal overdose cases involving heroin, fentanyl, methamphetamine, or cocaine. Substances found by death scene investigators at the scene of the fatal overdose (57 samples) were tested using high-pressure liquid chromatography mass-spectrometry (LC-MS) technology. We compared toxicology and LC-MS results to understand whether substances contributing to overdose were found in combination or separately at the scene of the overdose.Results: Comparing toxicology reports with LC-MS results from substances found at the scene of overdose deaths involving opioids and stimulants reveal that deaths are largely the result of the co-use of opioids and stimulants, rather than use of stimulants combined with opioids.Conclusions: Collecting and testing physical samples from fatal overdose scenes and comparing these to post-mortem toxicology results is a new way to examine polydrug use patterns. This community overdose surveillance method can be used to improve overdose prevention and response efforts. [ABSTRACT FROM AUTHOR]