Since the last review about the safety and efficacy of dexketoprofen trometamol, new clinical evidence supporting its advantages has been published. Concerning the oral formulation, studies about its pharmacokinetics in special populations and efficacy studies in various pain conditions are now available. Conversely, with the approval of a parenteral formulation, dexketoprofen trometamol nowadays has a wider scope of possible indications. Studies with the parenteral formulation have proven an analgesic efficacy similar to its comparators, an opioid-sparing effect, lower incidence of nausea and vomiting, better quality of sleep and lesser degree of sedation. Altogether, the overall benefit-risk ratio of both formulations in the approved indications remains positive. Its proven effectiveness and repeatedly demonstrated rapid onset of action combined with its safety profile make dexketoprofen trometamol an interesting alternative with greater versatility, and support its administration as a first-line painkiller.