Background: Delirium is a common concern among elderly intensive care unit (ICU) patients. Ketamine’s effectiveness in preventing delirium remains controversial despite its demonstrated neuroprotective properties and cognitive benefits in previous studies. Objectives: This study aimed to compare the safety and efficacy of ketamine and haloperidol in preventing delirium in elderly ICU patients. Methods: This randomized clinical trial involved 44 non-intubated patients aged over 65 years in a general ICU. The patients received low-dose intravenous ketamine (20 mg) or intramuscular haloperidol (2.5 mg). Delirium was assessed using the Richmond Agitation Sedation Scale (RASS) at 5, 10, and 15 minutes. The primary outcome was the percentage of patients achieving adequate sedation (RASS ≤ +1). The secondary outcome was time to reach adequate sedation. Adverse effects and physician satisfaction were evaluated after 60 minutes. Results: No significant difference in delirium was observed between the groups after interventions or within each group over time. However, the ketamine group had significantly lower delirium incidence at 5 minutes. The percentage of patients achieving adequate sedation was higher in the ketamine group (86.4%) than in the haloperidol group (36.4%) (P = 0.002). There was a delirium difference between groups at 10 minutes (P = 0.31) or 15 minutes (P = 0.082). Physician satisfaction did not differ significantly (P = 0.144). Conclusions: The present study suggests that the administration of low-dose ketamine to elderly ICU patients might reduce delirium incidence, supporting its beneficial effect for delirium control.