Background and Objectives: Soluble suppression of tumorigenicity-2 (sST2) is a biomarker associated with myocardial stress, inflammation, and fibrosis. Although elevated sST2 levels have demonstrated prognostic significance in heart failure and acute coronary syndromes, their clinical relevance in patients undergoing percutaneous coronary intervention (PCI) remains incompletely defined. This study aimed to evaluate the association between baseline serum sST2 levels and long-term clinical outcomes in an unselected real-world cohort of patients undergoing PCI. Materials and Methods: A total of 758 consecutive patients with coronary artery disease who underwent PCI between September 2015 and November 2017 were enrolled. Baseline serum sST2 levels were measured before PCI, and patients were stratified according to the median value (28.3 ng/mL). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), defined as a composite of cardiac death, nonfatal myocardial infarction, and nonfatal stroke. Multivariable Cox proportional hazards models and receiver operating characteristic analyses were performed to assess the association of sST2 with clinical outcomes and its discriminatory ability. Results: During a median follow-up of 28.3 months, MACCEs occurred in 19 patients (2.5%). Patients with higher sST2 levels had significantly higher rates of MACCEs (4.2% vs. 0.8%, p = 0.005) and all-cause mortality (11.9% vs. 2.6%, p < 0.001) than those with lower sST2 levels. Although the association between elevated sST2 and MACCE was attenuated after multivariable adjustment (adjusted hazard ratio, 3.28; 95% confidence interval, 0.91–11.83; p = 0.070), receiver operating characteristic analysis demonstrated moderate predictive performance for MACCE (AUC, 0.723) and all-cause mortality (AUC, 0.763). The optimal cutoff value for predicting MACCE was 52.2 ng/mL. Conclusions: Elevated baseline serum sST2 levels were associated with adverse long-term clinical outcomes in an unselected, real-world cohort of patients undergoing PCI. Further studies are warranted to clarify its prognostic role in this population.