The combined formulation of diclofenac/misoprostol provides effective relief of pain and inflammation, with a 2- to 3-fold lower incidence of NSAID-associated gastroduodenal ulcers than diclofenac monotherapy. Both components of the combined formulation have been widely used and have well documented efficacy and tolerability profiles. Compared with other agents used as prophylaxis for NSAID-induced gastropathies, misoprostol is generally considered to have the most extensive outcomes data establishing its efficacy in preventing both gastric and duodenal ulcers associated with long term NSAID use. Economic analyses conducted to date have shown that diclofenac/misoprostol is associated with similar or lower total direct medical treatment costs compared with other NSAIDs (with or without coprescribed misoprostol or an alternate prophylactic agent). As with pharmacoeconomic studies of coprescribed misoprostol with NSAIDs, the most favourable results with the combined formulation of diclofenac/misoprostol appear to be in patients at high risk of developing NSAID-associated gastroduodenal ulcers (e.g. the elderly). Although economic analyses with diclofenac/misoprostol were conducted in several different countries using a variety of methodologies and employing a wide range of clinical and economic assumptions, results have been generally favourable for the combined formulation. However, as is the case with pharmacoeconomic analyses in general, results of individual studies with diclofenac/misoprostol may not be generalisable between countries and are subject to change over time. Overall, clinical and economic data suggest that the optimal and most cost-effective use of the combined formulation of diclofenac/misoprostol is in patients requiring long term NSAID therapy who are at increased risk of developing NSAID-induced gastropathy, such as elderly patients with rheumatoid arthritis or osteoarthritis.