A method and system for non-invasive assessment of coronary artery stenosis is disclosed. Patient-specific anatomical measurements of the coronary arteries are extracted from medical image data of a patient acquired during rest state. Patient-specific rest state boundary conditions of a model of coronary circulation representing the coronary arteries are calculated based on the patient-specific anatomical measurements and non-invasive clinical measurements of the patient at rest. Patient-specific rest state boundary conditions of the model of coronary circulation representing the coronary arteries are calculated based on the patient-specific anatomical measurements and non-invasive clinical measurements of the patient at rest. Hyperemic blood flow and pressure across at least one stenosis region of the coronary arteries are simulated using the model of coronary circulation and the patient-specific hyperemic boundary conditions. Fractional flow reserve (FFR) is calculated for the at least one stenosis region based on the simulated hyperemic blood flow and pressure.
