Although stent implantation may be associated with tissue protrusion (TP), especially in patients with acute coronary syndrome (ACS), its long-term clinical outcomes remain unknown. The aim of the current study was to evaluate the long-term clinical outcomes of ACS patients with TP after the implantation of newer-generation drug-eluting stents (DESs). We retrospectively evaluated 366 consecutive ACS patients who underwent primary percutaneous coronary intervention (PCI) with newer-generation DESs. All culprit lesions underwent pre- and post-PCI intravascular ultrasound (IVUS) examinations and were classified according to the presence or absence of post-stent TP. After primary PCI, 198 lesions (54.1%) displayed TP on IVUS examination. At the 12-month follow-up, the incidence of target lesion revascularization did not differ between patients with (n = 198) and without (n = 168) TP (3.5 vs. 4.2%, p = 0.790). The incidence of recurrent ACS (r-ACS) was higher in patients with versus those without TP (7.1 vs. 2.4%; log-rank test p = 0.043). Cox proportional hazard analysis showed that triple-vessel disease (HR = 9.258, p = 0.001), TP (HR = 3.149, p = 0.008), and low-density lipoprotein cholesterol reduction rate ≥ 50% (HR = 0.184, p = 0.008) were the independent predictors of r-ACS. TP detected using IVUS after DES implantation may be associated with the occurrence of r-ACS after the 12-month follow-up, although short-term clinical outcomes were not worse during the 12-month follow-up.