Our current knowledge regarding the efficacy of factors stimulating collateral artery growth in the peripheral circulation primarily stems from models in small animals. However, experimental models in large sized animals are a prerequisite for extrapolation of growth factor therapy to patients with peripheral atherosclerotic obstructive disease. Therefore, we have developed a novel porcine femoral artery ligation model using non-invasive and invasive evaluation techniques. In 12 young farm pigs and nine older minipigs, a ligation of the superficial femoral artery was performed. Using an intra-arterial catheter, phosphate buffered saline (PBS) was administered with a first-pass over the collateral vascular bed. Directly after ligation as well as after 2 weeks of continuous infusion of PBS, perfusion of the leg was measured using various flow and pressure parameters. Using a pump driven extracorporal system, collateral conductance was determined under maximal vasodilatation. Conductance decreased after acute ligation to similar levels in both young farm pigs as well as the older minipigs (both 9.3% of normal perfusion) and recovered after 2 weeks to a higher value in farm pigs compared with minipigs (22.4 vs. 12.7% of normal; P<0.05). Angiography using both X-ray and magnetic resonance imaging was performed to visualize the formed collateral arteries. To the best of our knowledge this is the first in vivo pig model for hemodynamic assessment of growth of collateral arteries in the peripheral circulation, that is suitable for evaluation of arteriogenic effects of growth factors or genes.