Tapentadol is a novel, centrally acting analgesic with two mechanisms of action: micro-opioid receptor agonism and norepinephrine reuptake inhibition. It has demonstrated broad analgesic efficacy across multiple pain models. This article reviews the clinical development of tapentadol immediate release (IR), including results from Phase II and III clinical trials that evaluated the efficacy and safety of tapentadol IR in patients with moderate-to-severe acute pain. In clinical studies in patients with moderate-to-severe acute postoperative pain, osteoarthritis pain and/or low back pain, tapentadol IR 50, 75 or 100 mg every 4 - 6 h has demonstrated analgesic efficacy similar to that observed with the micro-opioid receptor agonist oxycodone HCl IR 10 or 15 mg every 4 - 6 h. However, at doses providing comparable analgesic efficacy, tapentadol IR has been associated with significantly lower incidences of nausea and/or vomiting and constipation, and a significantly lower rate of treatment discontinuation compared with oxycodone IR. The observed efficacy across different pain models and favorable gastrointestinal tolerability profile associated with tapentadol IR indicate that this novel analgesic is an attractive treatment option for the relief of moderate-to-severe acute pain.