Background: Ketamine is increasingly used in the United Kingdom in non-clinical settings for its psychoactive effects, with rising reports of harms including hospital admissions, dependence and deaths. In light of current debates surrounding the reclassification of ketamine under the Misuse of Drugs Act 1971, up-to-date surveillance of associated mortality is warranted.

Aims: We aimed to quantify trends in deaths following illicit ketamine use in England, Wales and Northern Ireland, and to examine changes in demographic and contextual characteristics since the last national analysis which comprised illicit ketamine deaths up to 2019.

Methods: Cases where illicit ketamine was detected at post-mortem were extracted from the National Programme on Substance Use Mortality and analysed.

Results: There were 696 deaths identified with illicit ketamine between 1999 and 2024. Annual deaths increased over 10-fold from 2014 (15 deaths) to 2024 (197 projected deaths). Whilst absolute deaths implicating illicit ketamine rose (2014: 6 deaths; 2023: 123 projected deaths), the proportion of deaths where illicit ketamine was implicated in causing death declined (2014: 60.0% of cases; 2024: 42.6% of cases). Concurrently, polydrug use increased (median number of co-administered substances 1999–2004: 3; 2005–2009: 3, 2010–2014: 4, 2015–2019: 6; 2020–2024: 6), and the demographic profile of decedents shifted towards greater deprivation and dependence-related contexts.

Discussion and Conclusions: There has been an acceleration in deaths following illicit ketamine in recent years, which are increasingly featuring complex patterns of polydrug use and socio-economic vulnerability. Policy responses must extend beyond single-substance legislative controls to encompass harm reduction, treatment integration, and social support strategies.