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The UK, as the "cocaine capital of Europe," currently accounts for ∼75% of all cocaine-related hospital admissions in Europe. This study aims to analyze the trends in cocaine-related deaths in England, Wales and Northern Ireland over 20 years (2000-2019). Cases reported to the National Programme on Substance Abuse Deaths (NPSAD) occurring between 2000 and 2019 where cocaine was detected at post-mortem (PM) were extracted for analysis. A total of 5,339 cases were retrieved, with an increase in the rate of reporting over time. Cocaine was deemed a cause of death and quantified in PM blood samples along with its major metabolite benzoylecgonine in 685 cases. Of these 685 cases, 25% (n = 170/685) occurred following acute use, 22% (n = 154/685) following chronic/binge use, 40% (n = 271/685) in combination with morphine, 4% (n = 29/685) in drug packer/swallower circumstances and 9% (n = 61/685) in a suicide context. Cardiac complications were evident in 22% of cases (n = 154/685). The average concentration of cocaine detected in cardiac cases (900 ng/mL) was considerably lower than that detected in cases where acute (19,100 ng/mL) or chronic/binge (6,200 ng/mL) dosing was evident. This is the first cocaine-related mortality study in these geographical areas. Deaths following cocaine use continue to rise despite its Class A drug listing in the UK. While underlying and external risk factors including polydrug use, cardiac complications and mental health can all contribute to the incidence of fatal drug toxicity following cocaine use, this study demonstrates that the risk of a cocaine overdose cannot be attributed to a specific blood concentration range., (© The Author(s) 2023. Published by Oxford University Press.)