Background <p>Many methods have been used in to treat low back pain. In this study, we aimed to investigate the efficacy of dexketoprofen alone and in combination with methylprednisolone in the treatment of low back pain in the emergency department using the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI).</p> Methods <p>This prospective, randomized, single-blind study included 150 patients admitted to the emergency department of a university hospital. Patients with low back pain were divided in to two groups: those receiving intravenous dexketoprofen treatment (Group D) and those receiving dexketoprofen + methylprednisolone treatment (Group DM). The efficacy of the treatments received by the patients was evaluated with the VAS at minutes 0, 15, 30, and 60 and hour 48. Statistical evaluations were also undertaken on the ODI results evaluated at minute 0 and hour 48.</p> Results <p>The VAS scores decreased in both groups at all follow-up evaluations performed throughout the treatment (<i>p</i> = 0.000). The mean VAS score evaluated 48&#xa0;h after treatment was 1.69 ± 1.71 (Median:1) cm in Group DM and 4.13 ± 2.27 (Median:4) cm in Group D (<i>p</i> = 0.000). The decrease in the ODI score was greater in Group DM than in Group D (<i>p</i> = 0.000).</p> Conclusion <p>Dexketoprofen showed analgesic efficacy in the treatment of non-traumatic low back pain and decreased disability. When combined with methylprednisolone, dexketoprofen treatment exhibit a greater analgesic effect and further reduced disability.</p> Trial registration <p>Current Controlled Trials NCT06932367 (Retrospectively registered).</p> Clinical trial number <p>Not applicable.</p>