Opioids have been endorsed as appropriate treatment for refractory chronic non-cancer pain when used according to published guidelines. They are widely used for this indication. However, there appear to be gaps in our understanding of the efficacy and safety of individual long-acting opioids compared to each other or as a class compared to short-acting opioids. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of long-acting opioids in the management of chronic non-cancer pain. Randomized trials (for comparative efficacy and adverse events) and observational studies (for adverse events only) that included non-parenteral long-acting opioids were sought using electronic databases, handsearching reference lists, and soliciting pharmaceutical company submissions. Searches were performed through October 2002. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 16 randomized trials (comparative efficacy and adverse events), enrolling 1427 patients, and 8 observational studies (adverse events) of 1190 patients were included in this review. No randomized trial was rated good quality; observational studies were generally of poorer quality than the trials. There was insufficient evidence to prove that different long-acting opioids are associated with different efficacy or safety profiles. There was also insufficient evidence to determine whether long-acting opioids as a class are more effective or safer than short-acting opioids. A subgroup of three studies on long-acting versus short-acting oxycodone was more homogeneous and provided fair evidence that these formulations are equally effective for pain control.