BACKGROUND: The diagnostic and prognostic roles of cardiovascular biomarkers in chronic coronary syndrome remain unclear. METHODS: Patients undergoing coronary angiography for suspected chronic coronary syndrome were prospectively enrolled (n=2251; median follow-up 12.6 years). Obstructive coronary artery disease was defined as ≥50% stenosis in ≥1 major epicardial vessel. HsTnT (high-sensitivity cardiac troponin T), NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity C-reactive protein, interleukin-6, and copeptin were measured. Receiver operating characteristic analysis and Cox regression with biomarker × treatment interaction testing were performed. RESULTS: Overall, 888 patients (39.4%) had obstructive coronary artery disease. Only hsTnT showed meaningful diagnostic capacity (area under the curve 0.669; risk factor-weighted clinical likelihood area under the curve 0.663), with incremental benefit inversely proportional to risk factor-weighted clinical likelihood category (Δ area under the curve: very low 10.4%, low 8.0%, intermediate/high 5.0%). NT-proBNP was the strongest mortality predictor across optimal medical therapy (hazard ratio [HR], 1.488 [95% CI, 1.288-1.720], P<0.001), percutaneous coronary intervention (HR, 1.220 [95% CI, 1.020-1.458], P=0.029), and coronary artery bypass grafting (HR, 1.220 [95% CI, 1.049-1.420], P=0.010). Interaction analysis validated a data-derived 150 pg/mL threshold (P=0.032): below it, mortality was comparably low regardless of revascularization (HR, 0.98 [95% CI, 0.67-1.43], P=0.910); above it, baseline risk was markedly elevated (HR, 5.75 [95% CI, 4.10-8.00], P<0.001) and revascularization associated with 40% mortality reduction, with substantial residual risk (HR, 3.43 [95% CI, 2.70-4.40], P<0.001). CONCLUSIONS: HsTnT provides risk factor-weighted clinical likelihood category-specific incremental diagnostic value. NT-proBNP is a universal prognostic marker identifying patients with distinct revascularization-associated mortality reduction driven by differential baseline risk. REGISTRATION: URL: https://clinicaltrials.gov/study/NCT00497887; Unique Identifier: NCT00497887.