Although blood is the most commonly used specimen in forensic toxicology, it is not always available. In those cases, alternative samples are sought on which to perform toxicology testing. The current study assessed the usefulness of synovial fluid for postmortem cocaine and opiate/opioid testing. One hundred four cases were sampled, with 98 cases being tested representing 24 negative controls and 74 cases positive for cocaine, benzoylecgonine, morphine, 6-monoacetylmorphine, hydrocodone, and/or oxycodone. Synovium demonstrated excellent correlation and predictability when compared with blood, although it was not as sensitive for 6-monoacetylmorphine as either vitreous or urine. The authors recommend further study to assess the usefulness of synovial fluid in postmortem toxicology to include the evaluation of its utilize for more drugs and the development of further assays to use its potential even in limited quantities.