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92 reviewsDespite advances in secondary prevention, adverse cardiovascular events still occur after acute myocardial infarction(AMI). Contributing to residual cardiovascular risk, acute and persistent inflammation is a stronger predictor of recurrentevents and mortality than low-density lipoprotein cholesterol. The inflammatory response following AMI is a finelyregulated, multiphase process, beginning with a proinflammatory phase followed by a reparative phase. Disruptions inits regulation lead to persistent low-grade inflammation and worse clinical outcomes. Modulating inflammation hasemerged as a promising secondary prevention strategy, with several drugs being tested with conflicting resultsregarding their efficacy and safety. Recently, novel approaches have reignited the interest in anti-inflammatory strategies after AMI. However, key knowledge gaps remain regarding potential class effects, drug choice, patient selection,and the optimal administration timing. This review provides an updated and comprehensive overview of inflammatorymechanisms after AMI and critically appraises the evolving clinical evidence surrounding anti-inflammatory therapies forsecondary cardiovascular prevention. (JACC. 2025;86:1146–1169) © 2025 by the American College of CardiologyFoundation.