Results of six systematic reviews (including one conventional meta-analysis and three network meta-analyses) and three individual RCTs suggest greater pain reduction and more adverse events with tramadol and tramadol combination products compared with placebo. The differences, however, were not always statistically significant. A network meta-analysis between tramadol and other active treatments suggests similar efficacy on pain relief between tramadol and NSAIDs, acetaminophen and other opioids. The results, however, need to be interpreted with caution as significant heterogeneity was observed across the individual studies included in the systematic reviews and meta-analyses. Results of individual RCTs showed similar pain relief and safety for tramadol compared with acetaminophen and NSAIDs in patients with acute pancreatitis, but tramadol was superior to desmopressin or indomethacin in patients with acute renal colic. For patients with osteoarthritis, transdermal fentanyl was superior to a tramadol plus acetaminophen combination in pain control. However, the quality of these trials may have been compromised and it remains uncertain whether the findings are generalizable to the Canadian population.