Objective: To compare the differences in long-term vascular structure and function after treatment with drug-coated balloons (DCB) versus drug-eluting stents (DES) in patients with hemodynamically stable acute coronary syndrome (ACS). Methods: This was a single-center retrospective cohort study. Patients admitted for ACS between November 2022 and June 2025, with Killip class 1–2, who underwent percutaneous coronary intervention (PCI) and completed 6–12 months of angiographic follow-up were consecutively enrolled. Patients with cardiac arrest, those requiring mechanical ventilation, or those with severe non-cardiovascular comorbidities were excluded. Based on the final interventional technique, patients were divided into the DES group (n = 62) and the DCB group (n = 42). The primary endpoint was late lumen loss (LLL) measured by quantitative coronary angiography (QCA). Secondary endpoints included coronary slow flow phenomenon (CSFP), coronary restenosis, and repeat revascularization during follow-up. Multivariable rank regression was used to adjust for confounding factors such as left ventricular ejection fraction (LVEF) and acute myocardial infarction (AMI) status. Results: After multivariable adjustment, the extent of LLL was significantly lower in the DCB group than in the DES group (β = 21.90, p < 0.001). Subgroup analysis demonstrated that this advantage persisted across different LVEF levels. Importantly, the incidence of CSFP was significantly lower in the DCB group than in the DES group (2.4% vs. 17.7%, p = 0.016). No statistically significant differences were observed between the two groups in terms of restenosis rate and repeat revascularization rate. Conclusion: In patients with hemodynamically stable ACS, the DCB interventional strategy demonstrates significant advantages over DES in suppressing LLL and preventing CSFP.