Background Structural alterations of aortic wall resulting from degradation of matrix proteins by matrix metalloproteinases (MMPs) characterize abdominal aortic aneurysms (AAAs). No studies have compared circulating levels of MMPs after endovascular graft (EVG) exclusion in comparison with open surgical repair (OSR) in patients affected by AAA. Methods and Results An abdominal angiography and CT scan were performed in all patients at the time of enrollment. A spiral CT scan was performed at 6 months to detect presence of endoleaks. MMP-3 and MMP-9 levels were measured before EVG (n=30) and OSR (n=15) treatments and at 1, 3, and 6 months of follow-up by a sandwich ELISA technique. Healthy volunteers (n=10) were used as control subjects. Immunohistochemical staining for MMP-9 and MMP-3 was performed on tissue samples from surgical cases. Both MMP-9 and MMP-3 mean basal levels were significantly higher in patients affected by AAA than in control subjects (32.3±20.7 ng/mL for EVG and 28±9.9 ng/mL for OSR versus 8.9±2.5 ng/mL, 2P<0.05; 18.3±9.7 ng/mL and 26.7±10.8 ng/mL versus 8.2±5.3 ng/mL, 2P<0.001). In the OSR group, both MMP-9 and MMP-3 mean levels decreased after surgery (28±9.9 ng/mL at basal versus 14.7±6.6 ng/mL at 6 months, 2P<0.001; 26.7±10.8 versus 12±5.3 ng/mL; 2P<0.001). In the EVG group, a statistically significant difference at 6-month follow-up in MMP-9 and MMP-3 mean plasma values was detected in patients who had endoleakage in comparison with patients without endoleakage (44.3±20.7 versus 14.6±7.0 ng/mL, 2P<0.005; 25±11.5 versus 10.3±5.4 ng/mL, 2P<0.005). Conclusions After EVG exclusion, MMP-9 and MMP-3 levels decreased to a level similar to that of patients undergoing OSR. In addition, a lack of decrease in MMP levels after EVG exclusion may help in identifying patients who will have endoleakage and consequent aneurysm expansion caused by continuous sac pressurization during follow-up.