Matrix metalloproteinase-9 (MMP-9) plays an important role in the onset and prognosis of myocardial infarction. Targets of angiotensin converting enzyme (ACE) inhibitors might include not only ACE but also MMP-9, and ACE seems to be closely associated with complications of hypertension such as cardiovascular remodeling whereas MMP-9 is closely related to coronary diseases. We postulate that ACE inhibitors prevent coronary diseases via direct MMP-9 inhibition and could interact with the MMP-9 active sites using specific modes similar to those used for the ACE active sites. Research of the molecular interaction between MMP-9 active sites and ACE inhibitors appears to be an important key in the development of effective MMP-9 inhibitors for cardiovascular protection.