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Introduction: Traumatic rib fractures (TFRs) carry an increased risk for hospitalization, morbidity, and mortality, it is essential to quickly initiate multimodal analgesic therapies. Both intravenous (IV) ketamine and lidocaine infusions have shown efficacy in treating patients with TRFs, however, no study has compared the effectiveness of these two agents in achieving analgesic control. Methods: Adult patients admitted to a Level 1 Trauma Center and diagnosed with three or more TRFs requiring hospital admission were included from April 2021 until September 2024. Patients were then randomized to receive either ketamine or lidocaine infusion based on the escalated medical need for an advanced multimodal pain management approach. All patients also received standard multimodal therapy and were monitored longitudinally for up to 72 hours. Results: The study included 62 patients completing at least 24 hours of study medication, 31 patients in the ketamine group and 30 in the lidocaine group. No significant differences were observed in OME consumption at 24 hours post medication initiation (38 vs. 48; p=0.22), 48 hours post medication initiation (55 vs. 53; p=0.90), or 72 hours post medication initiation (120 vs. 47; p=0.23). No differences in NPS were observed at 24, 48, or 72 hours post medication initiation. No inter-group differences were noted in any other secondary outcome, including the neuraxial anesthetic placement, hospital length of stay, or in-hospital morality. Adverse events occurred in 18 patients receiving ketamine and 17 receiving lidocaine, with no significant difference between groups (p=0.91). The most common adverse events reported were nausea, dizziness, hallucinations, and blurred vision. Conclusions: This is the first study comparing ketamine and lidocaine infusions as adjunctive analgesia for patients with TRFs. Results demonstrated no significant difference in opioid use or pain scores between the two groups at any time point or impacting any secondary outcomes. Therefore, both infusion strategies can be considered efficacious as a part of a multimodal analgesic approach following TRFs. These results may also prove to be more advantageous for centers where neuraxial blockade cannot be performed or where medication formularies are limited.