The National Association of Medical Examiners convened an expert panel to update the association's evidence-based recommendations for investigating and certifying deaths associated with opioids and other misused substances to improve death certificate and mortality data for public health surveillance. The recommendations are as follows: 1. Autopsy provides the best information on a decedent's medical condition for optimal interpretation of toxicology results, circumstances surrounding death, medical history, and scene findings. The panel considers autopsy an essential component of investigating apparent overdose deaths. 2. Scene investigation includes reconciling prescription information and medication counts. Investigators should note drug paraphernalia or other evidence of using intoxicating substances. 3. Retain blood, urine, and vitreous humor whenever available. Blood from the iliofemoral vein is preferable to blood from more central sites. 4. A toxicological panel should be comprehensive, including potent depressant, stimulant, and antidepressant medications. Detecting novel substances present in the community may require special testing. 5. When death is attributed to a drug or combination of drugs (as cause or contributing factor), the certifier should list the drugs by generic name in the autopsy report and death certificate. 6. The best classification for manner of death in an overdose without any apparent intent of self-harm is "accident."