Background: The use of ketamine, a controlled dissociative anesthetic, has become more widespread in recent years with recreational/nonmedical use increasing and ketamine becoming more widely available in clinics to treat depression.

Aims: We examined recent trends in adverse effects related to ketamine use.

Methods: US National Poison Control data were examined, focusing on ketamine exposures among those aged ⩾13 between 2019 and 2021 (n = 758). We examined quarterly trends in exposure and delineated correlates of patients experiencing a major adverse effect or death.

Results: The number of reported exposures increased 81.1% from 2019 Quarter 1 through 2021 Quarter 4, from 37 to 67 (p = 0.018). The majority of patients were male (57.1%), and the plurality of cases involved intentional misuse or "abuse" (39.5%), followed by suspected suicide attempt (19.7%) and unintentional exposure (18.9%). A fifth (19.6%) experienced a major adverse effect or death. A third (33.4%) co-used other drugs; the drugs most commonly co-used were benzodiazepines (14.6%), alcohol (10.3%), and opioids (8.7%). Co-use of gamma-hydroxybutyrate (GHB; adjusted prevalence ratio (aPR) = 3.43, 95% confidence interval (CI): 1.57-7.46) and opioids (aPR = 2.44, 95% CI: 1.46-4.08) was associated with increased risk for a major adverse effect or death, as was injection-only administration (aPR = 2.68, 95% CI: 1.21-5.92).

Conclusions: Although still rare, poisonings involving ketamine have increased in recent years. Polydrug use-particularly with opioids or GHB-appears to be a particular risk factor for more serious adverse effects. As prevalence of use increases, it is important to monitor adverse effects and co-occurring behaviors to inform timely prevention and harm reduction as needed.