Objective: Randomised clinical trials have demonstrated that rofecoxibhas a better gastrointestinal tolerability profile than conventionalnonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, whichresults in a reduced utilisation of gastroprotective agents (GPA).The aim of this study was to estimate, from the national healthcaresystem perspective, the total drug costs in patients switched fromNSAIDs plus GPAs to rofecoxib. Design: In this longitudinal, observationalstudy, drug prescriptions for symptomatic treatment of osteoarthritiswere recorded. A decision tree was used to compare the mean dailydrug cost of the following therapeutic options for ostheoarthritis:conventional NSAIDs and rofecoxib/conventional NSAIDs. Setting: AziendaUnità Sanitaria Locale 110, Ravenna, Italy. Patients: 56,827 patientsaffected by osteoarthritis were monitored from January 1997 to December1999. Of this group, we considered the first 2,935 patients who wereexamined by 21 General Practitioners in the period July 2000-October2000, in order to point out changes in GPAs co-prescription afterthe introduction of rofecoxib in the Italian market. Interventions:Alternative treatments compared were: NSAIDs either alone or combinedwith GPAs (NSAIDs option), and just after the introduction of rofecoxib,NSAIDs or rofecoxib alone and NSAIDs or rofecoxib combined with GPAs(rofecoxib/NSAIDs option). Main outcome measures and results: 27,511out of 56,827 patients (48.4%; IC 95%: 48.0-48.8%) treated with NSAIDsalso received a GPA co-medication. In the aforementioned subgroupof 2,935 patients, 1,814 (62%) received multiple prescriptions ofNSAIDs or rofecoxib. In this subgroup, rofecoxib was associated witha statistically significant reduction of GPAs utilisation of 58.8%(IC 95%: 30.7-80.1; p = 0.012) compared with what was recorded duringtreatment with NSAIDs. In fact, the mean daily cost per patient ofthe NSAIDs option was € 1.66 versus € 1.55 of the rofecoxib/NSAIDsoption (6.6% lower). Conclusions: Our preliminary results suggestthat the use of rofecoxib is associated with cost savings in termsof total drug costs compared with conventional NSAIDs.