The conventional rationale that uses per cent diameter reduction to assess diffuse coronary artery disease is not appropriate because no normal reference segments exist. In a recent publication, we have proposed a theoretical model based on physical principles that relate the various morphological and haemodynamic parameters (cross-sectional area, length, volume and flow) of the normal coronary arterial tree. The model was validated using haemodynamic simulations based on detailed morphological data of the pig coronary arterial tree. This paper extends the model validation to in vivo swine studies. Coronary arteriography was performed in five swine (15–18 kg body weight) after power injection of contrast material into the coronary artery. Coronary arterial length was obtained using a 3D reconstruction technique. The arterial volume, cross-sectional area and blood flow were measured using videodensitometry. The proposed relationships between these quantities were validated. Furthermore, a sensitivity analysis was demonstrated based on a simulation of diffuse coronary artery disease (approximately 40% reduction in cross-sectional area). The results of a sensitivity analysis based on a simulation of diffuse coronary artery disease suggest that the relationships between arterial volume, cross-sectional area, blood flow and the distal arterial length can be utilized to quantify moderate levels of diffuse coronary artery disease.