Etizolam is a novel psychoactive substance and novel benzodiazepine of the 
thienotriazolodiazepine class, which has recently seen an increasing trend in 
use worldwide. We report a case series of 10 decedents with etizolam and opioids 
in their systems. Death investigation, expanded toxicology and medical 
investigation information were included for contextualization of etizolam in 
death. Etizolam was detected and confirmed within peripheral and cardiac blood, 
urine, vitreous humor and, in one case, gastric fluid, by liquid 
chromatography-tandem mass spectrometry and liquid chromatography-quadrupole 
time of flight mass spectrometry methodologies. Death investigation indicated 
nonmedical use of most drugs. Medical investigation commonly noted pulmonary 
edema, cardiomegaly and cerebral swelling. The majority of the decedents 
appeared to be unaware of the presence of etizolam and succumbed to the mixed 
drug toxicity of their routine depressant and narcotic analgesic drug of abuse 
in combination with etizolam. Etizolam use continues to be observed and poses as 
a potentially lethal contribution to multiple drug toxicity, especially in the 
age of the opioid crisis. Assessment of analytes like etizolam requires 
up-to-date methodologies and vigilance in testing to better characterize the 
toxicology and interpret the contribution to death.