Tapentadol (Nucynta) is an orally active, centrally acting synthetic analgesic that is thought to exert its analgesic effects via two mechanisms of action (mu-opioid receptor agonism and norepinephrine reuptake inhibition). In the US, the immediate-release (IR) formulation of the drug is approved for the relief of moderate to severe acute pain in patients aged > or =18 years. In the EU, the drug is currently in the marketing authorization process. In clinical trials in patients with moderate to severe acute (postorthopaedic surgical or musculoskeletal) pain, recommended regimens of tapentadol IR (50-100 mg every 4-6 hours) provided an analgesic effect that was superior to that of placebo, and noninferior or similar to that of oxycodone IR (10 or 15 mg every 4-6 hours). Tapentadol IR therapy was generally well tolerated; it was associated with significant reductions in the incidences of nausea, vomiting and constipation compared with oxycodone IR therapy. Thus, tapentadol IR is an effective treatment option for the management of moderate to severe acute pain. However, further studies evaluating its clinical utility in relation to that of tramadol and opioids other than oxycodone are warranted. Because tapentadol IR offers the prospect of reduced opioid-related gastrointestinal adverse events while maintaining adequate analgesia, it is a potentially valuable addition to the analgesic armamentarium.