For a study, researchers sought to determine the analgesic efficacy of oral VTS-Aspirin® (Vitalis Analgesics, New York, NY) and ketamine in adult emergency department (ED) patients with acute Musculoskeletal (MSK) pain. The analgesic efficacy of a single dose of the oral combination of VTS-Aspirin and ketamine in adult ED patients with acute moderate-to-severe MSK pain was evaluated in this prospective, proof-of-concept, single-arm pilot trial. The primary outcome was the difference in pain scores on an 11-point numeric pain rating scale at 60 minutes. The requirement for rescue analgesia, the occurrence of adverse events at 60 minutes, and a change in pain levels at 120 minutes were all secondary outcomes. The study had a total of 25 participants. The mean pain score at the start was 8.6, dropping to 4.8 after 60 minutes. The average oral ketamine dose was 37.8 mg, ranging from 24 to 50 mg. There were no clinically significant changes in vital signs. There were no major adverse effects in any of the participants. The majority of the negative effects were mild and temporary. Adhering to an oral combination of VTS-Aspirin and ketamine to adult ED patients with acute MSK pain resulted in clinically substantial pain reduction in 80% of enrolled participants, according to the outcomes.