OBJECTIVE To determine the efficacy and safety of opioid analgesics in inflammatory arthritis (IA). METHODS We searched Medline, Embase, and Central to May 2010. Randomized controlled trials in adults with IA that compared opioids (administered via any route) to another intervention or placebo were included. Studies in the immediate postoperative setting were excluded. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events (AE). Categorical data were pooled using RevMan5 and reported as relative risks (RR) or odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS Eleven studies were included, all in patients with RA. The risk of bias of all studies was high. No study was longer than 6 weeks in duration and 4 studies used single doses of study drugs. Seven studies were between 1 and 6 weeks in duration and assessed 6 different oral opioids. Only 1 study investigated a strong opioid. Data could be pooled from 4 studies comparing weak opioids to placebo: there was no difference in withdrawals due to inadequate analgesia (RR 0.82, 95% CI 0.34, 2.01), but patient-reported global impression of change was superior with opioids (RR 1.44, 95% CI 1.03, 2.03). Opioids were more likely than placebo to cause AE (OR 3.90, 95% CI 2.31, 6.56). There was no difference between opioids and placebo in net efficacy after adjustment for AE. CONCLUSION Based on 11 heterogeneous studies of short duration and high risk of bias, there is weak evidence that opioids are effective analgesics in RA. AE are common and may offset the benefits. The relative risks and benefits of opioids in IA beyond 6 weeks are unknown. ; Samuel L. Whittle, Bethan L. Richards, Désirée M. van der Heijde, and Rachelle Buchbinder