On September 30, 2004, because of an observed increased risk of serious cardiovascular (CV) events, Merck & Co, Inc, voluntarily withdrew rofecoxib from the worldwide market. The withdrawal has focused attention on the possible class effect on the cardiovascular system of the other currently available cyclooxygenase-2 (COX-2) selective inhibitors: celecoxib and valdecoxib. This review evaluates and differentiates the CV effects of COX-2 selective inhibitors through an assessment of prospective, randomized epidemiologic studies and meta-analyses.