Abstract: The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills (CDDP) in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction (AAMI). Between February 2021 and February 2023, 247 eligible patients with AAMI after primary percutaneous coronary intervention were enrolled and randomly assigned (1∶1) to receive CDDP (n = 126) or placebo (n = 121), with a follow-up of 48 weeks. Compared with the placebo group, the CDDP group demonstrated a significant increase in left ventricular ejection fraction values after 24 weeks of treatment (least squares mean: 3.31; 95% confidence interval CI: 1.72–4.90; P < 0.001) and at the 48-week follow-up (least squares mean: 4.35; 95% CI: 2.76–5.94; P < 0.001). Significant reductions in N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24- and 48-week visits with no significant difference between the two groups (P > 0.1 for all). The incidence of major adverse cardiovascular and cerebrovascular events was 6.35% in the CDDP group and 5.79% in the placebo group (P = 0.822). Notably, no serious adverse events were attributed to CDDP. These findings suggest that CDDP may be well tolerated and could improve left ventricular ejection fraction in patients with AAMI at 24 and 48 weeks.