Background <p>Mineralocorticoid receptor antagonists (MRA) have proven efficacy in heart failure and post-infarct left ventricular dysfunction, but their broader impact in acute coronary syndrome (ACS) remains uncertain.</p> Methods <p>We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing MRA versus placebo in patients following ACS. The primary endpoint was a composite of cardiovascular death, heart failure, or significant arrhythmia. Secondary endpoints included individual cardiovascular outcomes, recurrent myocardial infarction, stroke, all-cause mortality, ventricular remodeling parameters, and adverse events. PROSPERO registry CRD420251149760.</p> Results <p>Nine trials with 16,882 patients were included. Treatment with MRA significantly reduced the risk of the composite cardiovascular endpoint (RR 0.89, 95% CI 0.83–0.96; <i>p</i> = 0.001). This effect was primarily driven by reductions in cardiovascular mortality and heart failure events; no significant effect was observed for arrhythmias. Also, MRA lowered all-cause mortality (RR 0.88, 95% CI 0.80–0.97; <i>p</i> = 0.009) and improved left ventricular remodeling indices (increase in LVEF, reductions in LVESV/LVEDV). MRA did not significantly affect recurrent myocardial infarction or stroke. Safety analysis showed an increased risk of hyperkalemia (RR 2.14, 95% CI 1.45–3.16; <i>p</i> &lt; 0.001) but no significant differences in overall or serious adverse events versus placebo.</p> Conclusions <p>In patients with ACS, MRA therapy confers a significant reduction in composite cardiovascular events and all-cause mortality, with favorable remodeling effects and a safety profile consistent with known risks (notably hyperkalemia). These results support guideline-aligned use of MRA in post-ACS management, with appropriate monitoring strategies.</p> Graphical Abstract <p></p>