Hydrocodone is a semisynthetic opioid medication that is widely used as an analgesic and antitussive. Since 2004 it has been the most commonly prescribed drug in the United States and is often misused as a drug of abuse. Hydrocodone is frequently encountered in the postmortem setting, both as a cause of death and incidentally. Unfortunately, information regarding the concentrations of hydrocodone found with chronic high-dose use is lacking, and interpretation of postmortem concentrations can be difficult. A retrospective review of postmortem and "Driving under the Influence" (DUI) cases in Bexar County Texas in which hydrocodone was present was conducted. The cases were included in the study if they fit the criteria of belonging to 1 of 3 categories: the hydrocodone either caused or was the main contributor to death; the hydrocodone was incidental and definitively did not cause or contribute to death; and the DUI cases. The average hydrocodone concentration in the cases where the hydrocodone caused death was 0.47 mg/L (median, 0.38 mg/L). The average hydrocodone concentration in cases where it was incidental to death was 0.15 mg/L (median, 0.08 mg/L). The average hydrocodone concentration in the DUI cases was 0.09 mg/L (median, 0.08 mg/L). Analysis showed the possibility of postmortem redistribution as well as significant overlap of the concentrations noted in the different groups. Given that no definitive lethal concentration could be delineated, it is recommended that each hydrocodone case encountered be assessed individually to include a thorough medical record review to accurately interpret hydrocodone concentrations. It has also been shown that concentrations as high as 0.3 mg/L peripherally and 1.4 mg/L centrally can be present and not result in death. In addition, further research into hydrocodone concentrations with chronic use and hydrocodone metabolism is necessary.