Background: We have reviewed opioid-related adverse events in studies of opioid sparing with cyclooxygenase-2 (COX-2) inhibitors compared with placebo in postoperative pain. Methods: Randomized, controlled trials were evaluated. Outcome measures were significant reduction in consumption of supplementary opioids with the COX-2 inhibitors and reported opioid-related adverse events (nausea, vomiting, constipation, dizziness, sedation, pruritus and/ or urinary retention) 0-24 h after surgery. Results: Nineteen studies including 26 comparisons of four COX-2 inhibitors (rofecoxib, celecoxib, parecoxib and valdecoxib) were evaluated, in which significant opioid-sparing averaging about 35% with COX-2 inhibitors and opioid-related adverse events were reported. The trials were in general of high quality (median Oxford quality score 4) but the reporting quality of adverse events was poor. Opioid-related adverse events, i.e. vomiting, constipation and pruritus, were only significantly reduced with COX-2 inhibitors in four of the 26 comparisons. Quantitative analysis of combined data revealed a significantly reduced risk for only dizziness; the clinical relevance was minor as the number needed to treat (NNT) was about 33. Conclusion: The limitation of this review is the lack of quality of data of adverse events from the original trials. Although supplementary opioid consumption in all trials was significantly reduced by on average 35% with the COX-2 inhibitors, it was only sporadically possible to demonstrate a clinically important reduction in opioid-related adverse events. Data did not support the common opinion that opioid-sparing with COX-2 inhibitors provides much clinical beneficial effect with respect to opioid-related adverse events. Future studies have to increase the awareness and proper reporting of adverse events in the postoperative period.