The collection of blood and tissue provides an opportunity for an objective comparison of autopsy results. Occasionally, a viable tissue sample is not available during autopsy. Expanding upon collected tissues to include a tissue that is accessible, is a possible drug depot, and is amendable to various analytical techniques may complement information obtained from other specimens. Given its absorption of ions, nutrients, and likely drugs via its rich blood supply, we evaluated the use of submandibular salivary gland tissue as an alternative postmortem specimen. The submandibular salivary glands of 52 decedents were excised. The tissue was homogenized, extracted, and analyzed via liquid chromatography tandem mass spectrometry for 43 opioids and 5 nonopioids. Liquid chromatography tandem mass spectrometry salivary tissue results were compared with the decedent's blood results. Results revealed that opioids were detected in salivary gland tissue at a sensitivity and specificity of 94.4% and 94.1%, respectively. Nonopioid drugs were detected at a sensitivity and specificity of 88.2% and 100.0%, respectively. This study suggests a comparable correlation exists between salivary gland tissue and blood results for certain drugs. Further evaluation is warranted. To our knowledge, this is the first report of salivary gland tissue being used for postmortem toxicology testing in humans.