Objective: Acute pain associated with injuries (i.e., sprains, strains, contusions, and low back pain) is treated with non-steroidal anti-inflammatory drugs (NSAIDS) or topical anesthetics. These agents vary in effectiveness, may have gastrointestinal and cardio-renal side effects, and possibly interact with other systemic medications. Diclofenac epolamine topical patch (DETP) is a treatment option with minimal systemic absorption, low risk of adverse drug-drug interactions, and local anti-inflammatory properties. This analysis was designed to determine the cost-effectiveness of DETP versus lidocaine patch in the treatment of acute pain. Methods: A decision analysis methodology was utilized to develop a model which served as an analytical decision support tool, where the expected values of the competing agents were calculated and compared. Published data was used to populate the efficacy and adverse event probabilities for treatment with DETP and lidocaine patch. We adjusted costs to 2007 dollars and used each drug's average daily cost (ADC), as well as overall medical care costs associated with various outcomes. The ADC in this analysis for DETP and lidocaine patch was $7.65 and $14.08, respectively. Results: The total drug costs for a two-week duration of DETP and lidocaine patch were $107.10 and $197.12, respectively. The total health care costs (office visits and additional medical services) for therapy with DETP and lidocaine patch were $290.22 and $380.53, respectively. The 2-week course of therapy yielded a resultant cost-effectiveness of $401.42 for DETP and $556.34 for lidocaine patch. When the treatment timeframe was evaluated for 30 days, the cost-effectiveness for DETP and lidocaine patch was $551.31 and $885.69, respectively. Conclusion: Although further validation is warranted and future studies may need to be expanded to include other agents, preliminary results demonstrate that the DETP may represent a cost-effective alternative to lidocaine patch in the management of acute pain.