This systematic review and meta-regression analysis evaluates the effectiveness of β-blockers in short-term treatment for acute myocardial infarction (AMI) and long-term secondary prevention. The study aims to assess predictive factors influencing outcomes and the clinical importance of the results in light of current treatments. The review includes 82 randomized controlled trials with data on all-cause mortality, focusing on both short-term (up to 6 weeks) and long-term (6 to 48 months) treatments. Overall, β-blockers showed a 23% reduction in the odds of death in long-term trials but only a 4% reduction in short-term trials. Meta-regression analysis found no significant reduction in effectiveness for cardioselective drugs but suggested a near-significant trend towards decreased benefit for drugs with intrinsic sympathomimetic activity. Propranolol, timolol, and metoprolol were the most studied drugs, with propranolol and timolol showing the most significant reductions in the odds of death. The number needed to treat for 2 years to avoid one death was 42, which is favorable compared to other treatments for AMI patients. The study concludes that β-blockers are effective in long-term secondary prevention but are underused, leading to avoidable mortality and morbidity.This systematic review and meta-regression analysis evaluates the effectiveness of β-blockers in short-term treatment for acute myocardial infarction (AMI) and long-term secondary prevention. The study aims to assess predictive factors influencing outcomes and the clinical importance of the results in light of current treatments. The review includes 82 randomized controlled trials with data on all-cause mortality, focusing on both short-term (up to 6 weeks) and long-term (6 to 48 months) treatments. Overall, β-blockers showed a 23% reduction in the odds of death in long-term trials but only a 4% reduction in short-term trials. Meta-regression analysis found no significant reduction in effectiveness for cardioselective drugs but suggested a near-significant trend towards decreased benefit for drugs with intrinsic sympathomimetic activity. Propranolol, timolol, and metoprolol were the most studied drugs, with propranolol and timolol showing the most significant reductions in the odds of death. The number needed to treat for 2 years to avoid one death was 42, which is favorable compared to other treatments for AMI patients. The study concludes that β-blockers are effective in long-term secondary prevention but are underused, leading to avoidable mortality and morbidity.