This study aimed to investigate the combined efficacy in prediction of major adverse cardiac events (MACE) by coronary regional physiological indices including coronary flow reserve (CFR) or fractional flow reserve (FFR) and high-sensitivity cardiac troponin-I (hs-cTnI) or N-terminal pro brain natriuretic peptide (NT-proBNP). Impaired CFR, decreased FFR, elevated cardiac troponin, and NT-proBNP are all associated with increased MACE, while these interaction or collinearity remains uncertain. The study included 429 patients with stable coronary artery disease (CAD) evaluated hs-cTnI and NT-proBNP levels before regional physiological measurement during coronary angiography. Patients were followed up for MACE including all-cause death, myocardial infarction, hospital admission for heart failure and target vessel remote revascularization. Median hs-cTnI and NT-proBNP values were 4 ng/L and 85 ng/L, respectively. Regional CFR was significantly albeit weakly correlated with hs-cTnI and NT-proBNP, while fractional flow reserve (FFR) was only linked to hs-cTnI. The addition of hs-cTnI and NT-proBNP on clinical backgrounds and angiographic score significantly improved predictive accuracy for MACE incidence, and further consideration of FFR and CFR could refine the model. The combined stratification using hs-cTnI, NT-proBNP, FFR and CFR could efficiently stratify patient risk for MACE. In patients with stable CAD, integrated assessment of cardiac biomarkers and physiological indices could be useful for predicting future cardiovascular events.