Background <p>Acute myocardial infarction (AMI) is one of the main causes of global morbidity and mortality. Stem cell-based therapy offers a promising approach for myocardial regeneration and tissue repair. Among them, bone marrow-derived stem cells (BMSCs) have shown remarkable therapeutic benefits in various clinical scenarios. Therefore, this study aimed to systematically evaluate the efficacy and safety of BMSCs in patients with AMI.</p> Methods <p>The computer retrieved the Cochrane Library, PubMed, Web of Science and Wiley Online Library databases, collected the randomized controlled trials on BMSCs for the treatment of AMI published in October 2025, and conducted data analysis using RevMan 5.4 and Stata 18.0.</p> Results <p>We enrolled 25 trials with 1822 patients, 960 patients in the BMSCs group, and 862 patients in the conventional treatment group. Meta-analysis findings indicated that BMSCs transplantation significantly enhanced left ventricular ejection fraction (LVEF) of patients with AMI relative to controls (MD = 2.45, 95% CI: 1.39 to 3.51) and reduced wall motion score index (WMSI) (SMD = -0.32, 95% CI: -0.49 to -0.15). For left ventricular end-diastolic volume (LVEDV) (SMD = -0.01, 95% CI: -0.16 to 0.13), left ventricular end-systolic volume (LVESV) (SMD = -0.04, 95% CI: -0.13 to 0.06) and myocardial infarct size (SMD = 0.01, 95% CI: -0.14 to 0.15), there was a trend toward improvement after infusion of BMSCs, but the difference was not statistically significant. In terms of safety, BMSCs transplantation did not increase the risk of major adverse cardiovascular events (MACEs) (OR = 0.80, 95% CI: 0.57 to 1.12).</p> Conclusion <p>BMSCs can effectively improve cardiac function in patients with AMI and demonstrate a favorable safety profile. However, their effect on ventricular remodeling remains uncertain, warranting further high-quality evidence to assess long-term outcomes.</p> Trial Registration <p>CRD420251147871.</p>