Acute and chronic inflammation play a central role in the pathophysiology of atherosclerosis. Corticosteroids are the gold standard anti-inflammatory agent and may have a role in treating acute myocardial infarction. However, concern exists regarding the potential for impaired wound healing and wall thinning. The MEDLINE and PreMEDLINE databases were searched for articles from 1966 through May 2002. A total of 186 articles and 16 English-language publications were identified. A meta-analysis of mortality in controlled trials was performed. Sensitivity analyses and 2 tests for publication bias were used to test the robustness of the results. Sixteen studies involving 3,793 patients were reviewed. Most studies were small (<100 patients) and revealed conflicting efficacy using surrogate outcome measures, such as infarct size. No clear association with myocardial rupture was observed. Meta-analysis of 11 controlled trials (2,646 patients) revealed a 26% decrease in mortality with corticosteroids (odds ratio 0.74, 95% confidence interval [CI] 0.59 to 0.94; p = 0.015). Sensitivity analyses limited to large studies and randomized controlled trials revealed odds ratios of 0.76 (95% CI 0.53 to 1.09) and 0.95 (95% CI 0.72 to 1.26), respectively. Two tests revealed no evidence for publication bias. Thus, the review of available clinical studies demonstrated no harm and a possible mortality benefit of corticosteroids in acute myocardial infarction.