A system for sealing a large penetration in the wall of a femoral artery comprises an occlusion catheter and an applicator. An access catheter may further be provided in order to facilitate introduction of the occlusion catheter. The occlusion catheter is introduced through a contralateral penetration, advanced over the aortic bifurcation, and an occlusion element on the occlusion catheter is positioned at the large diameter penetration. The occlusion element is then inflated to temporarily seal the large penetration while blood perfusion past the occlusion element is provided by the catheter. A sealing material, such as a tissue adhesive or other hemostatic agent is then introduced into a tissue tract above the large diameter penetration in order to seal the penetration. The occlusion element may be left in place while the sealing material has time to set, cure or otherwise form a permanent seal of the large penetration. The occlusion catheter and all access sheaths may then be removed from the patient.