© 2015 Academic Forensic Pathology International. Objective: To evaluate the association between death due to drug overdose and a history of laminectomy. Design: A retrospective matched case-control study of 234 drug overdose decedents from the Jefferson County Coroner/Medical Examiner's Office in Birmingham, Alabama were matched 1:2 on age to a control group consisting of decedents with any manner of death (accident, natural, suicide, homicide, or undetermined). Laminectomy cases were identified by the presence of a linear surgical scar near the spine in an orientation and place typical for a laminectomy. Results: Decedents whose cause of death was a drug overdose were 2.43 times (95% confidence interval [CI] 1.37-4.31) more likely to have a laminectomy scar compared to decedents in a control group consisting of all manners of death. This association held for males (odds ratio [OR] 2.34; 95% CI: 1.09-5.04) and whites (OR 2.35; 95% CI 1.06-5.18) after stratification. Conclusion: In the absence of an obvious cause for death, the presence of a laminectomy scar suggests the possibility of a fatal overdose and is a factor to consider in favor of performing an autopsy and toxicological analysis for drugs of abuse.