Previous studies have shown that the selective cyclo-oxygenase 2 inhibitors (COXIBs), rofecoxib and celecoxib, were as effective as conventional NSAIDs in relieving both pain and inflammation. In two prospective studies, each including more than 8000 patients, the use of COXIBs was associated with a clinically significant decrease in symptomatic ulcers and their complications (PUBs). In the VIGOR study, the annual incidence of PUBs was 2.1% in the rofecoxib group and 4.5% in the group treated with conventional NSAIDs (relative risk (RR): 0.5; 95% CI: 0.3-0.6). In the CLASS study, comparable results were observed: annual incidence of PUBs was 2.1% in the celecoxib group and 3.5% in the NSAID group (RR: 0.6; 95% CI: 0.4-0.9). In patients using low dose aspirin for cardio-protection, there was no difference between celecoxib and NSAIDs with respect to the incidence of PUBs. The use of rofecoxib was associated with a reduction in endoscopies, additional proton pump inhibitors and hospital admissions. In conclusion, COXIBs are a major advance in the prevention of ulcers and their complications for patients who require treatment with NSAIDs.