Background <p>Effective control of psychotic symptoms and behavioral problems is crucial in forensic psychiatric settings to enhance recovery and manage different risk concerns. While antipsychotic polypharmacy is commonly employed to ensure symptom control and risk mitigation, there is limited research on its burden and relationship with violent and aggressive behaviors in forensic psychiatric populations.</p> Objectives <p>This study aims to examine the prevalence of antipsychotic polypharmacy among forensic psychiatry patients in Ontario and assess its relationship with recent incidents of aggression and violence.</p> Methods <p>We conducted a retrospective analysis using a database prepared from data captured in annual reports submitted to the Ontario Review Board by 12 forensic programs in Canada. We utilized statistical analyses based on negative binomial regression to evaluate associations between antipsychotic polypharmacy and incidences of violence.</p> Results <p>Among 1,104 patients in the databases, 37.8% (<i>n</i> = 417) were on antipsychotic polypharmacy. The most frequent combination was with Olanzapine or Quetiapine. Antipsychotic polypharmacy was more likely among individuals with increased incidents of physical violence to objects (adjusted incidence rate ratio [IRR]: 1.69; 95% Confidence Interval [CI]: 1.07–2.68; <i>p</i> = 0.025), self-harm (IRR: 3.30; 95% CI: 1.29–8.44; <i>p</i> = 0.013), and sexually inappropriate behavior (IRR: 2.43; 95% CI: 1.35–4.36; <i>p</i> = 0.003) and aggression (IRR: 1.57; 95% CI = 1.10–2.27; <i>p</i> = 0.014).</p> Conclusions <p>Antipsychotic polypharmacy is prevalent among forensic psychiatry patients, and more likely among those with violent and aggressive behaviors. These findings underscore the need for innovative approaches and further research to inform clinical guidelines, thereby improving patient safety and treatment efficacy.</p> Clinical trial number <p>Not applicable.</p>