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Objective This meta-analysis evaluated the efficacy and safety of nesiritide in patients with acute myocardial infarction (AMI) and heart failure. Methods PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through December 2018. Studies including patients with AMI and heart failure who received nesiritide were identified. Results Ten trials involving 870 participants were included in this meta-analysis. Nesiritide treatment significantly increased left ventricular ejection fraction, cardiac index, and 24- and 72-hour urine volumes. Additionally, pulmonary capillary wedge pressure, right atrial pressure, and brain natriuretic peptide and N-terminal brain natriuretic peptide levels were significantly decreased in patients treated with nesiritide compared with those treated with control drugs. However, patients treated with nesiritide did not have an increased risk of mortality compared with those treated with control drugs. There were no differences between the two groups with respect to heart rate or the risk of readmission, hypotension, or renal dysfunction. Conclusions Nesiritide appears to be safe for patients with AMI and heart failure, and it improves global cardiac and systemic function.