AbstractAimsTo (i) assess the population mortality rates of cocaine‐related deaths in Australia, 2000 to 2021; (ii) determine the circumstances of death and case characteristics; and (iii) determine their toxicological profile.DesignRetrospective study of cocaine‐related deaths in Australia, 2000 to 2021, retrieved from the National Coronial Information System.SettingAustralia‐wide.CasesA total of 884 cases, mean age = 33.8 (SD, 10.0) years and 86.5% (n = 765) male.MeasurementsInformation was collected on characteristics, manner of death and toxicology. Only cases in which the presence of blood cocaine and/or metabolites were included.FindingsPopulation rates did not significantly increase during 2001–2011 (annual percentage change [APC] = 1.5; CI, −3.2, 6.5), but from 2012, there was a marked acceleration (APC = 20.0, 95% CI, 15.5, 25.3). Circumstances of death were unintentional drug toxicity (70.7%, n = 625), intentional self‐harm (17.8%, n = 157), traumatic accident (11.5%, n = 102). The proportion of cases constituted by unintentional toxicity declined across the study period (APC = −2.6; CI, −3.1, −2.1). There was a substantial decline in the proportion of cases with a history of injecting drug use (APC = −5.7; CI, −6.5, −4.9) and with a history of substance use problems (APC = −3.2; CI, −3.9, −2.5). Both cocaine (0.100 vs 0.050 mg/L, P < 0.001) and benzoylecgonine (0.590 vs 0.240 mg/L, P < 0.001) concentrations were higher amongst toxicity cases than in cases of death from traumatic injury. Cocaethylene was present in 26.4% (n = 233), levamisole in 18.6% (n = 164) and lignocaine in 11.5% (n = 102). Psychoactive drugs in addition to cocaine were present in 92.9% (n = 821), most commonly opioids (50.5%, n = 446), alcohol (47.1%, n = 416), hypnosedatives (43.2%, n = 382) and psychostimulants (30.3%, n = 268). There was a steady decline in the proportion of opioid positive cases (APC = −5.4; CI, −6.3, −4.5).ConclusionsThere was a large increase in cocaine‐related deaths across Australia from 2000 to 2021. This was accompanied by changes in case profiles, with histories of injecting drug use and substance use problems, as well as recent opioid use, becoming less prominent.