The common history of drug abuse in adults with an undetermined cause of death has led us to hypothesize that chronic drug abuse increases the risk of sudden death. To begin evaluating this hypothesis, we conducted a retrospective case-control study of 61 decedents whose cause of death remained undetermined following autopsy matched one to one to a control group of pedestrians or passengers killed in motor vehicle collisions. In 21 pairs, the case subject had evidence of drug abuse but the control did not, and in 5 cases the reverse was true. Analysis showed that individuals with an undetermined cause of death are 4.2 times more likely to have evidence of drug abuse than are victims of a motor vehicle collision. Copyright © 2005 by ASTM International.