OBJECTIVE: Intimal hyperplasia (IH) threatens the patency of up to 35% of saphenous vein (SV) bypass grafts. In addition to reducing cholesterol levels, statins may modulate smooth muscle cell proliferation and migration. Statins inhibit matrix metalloproteinase (MMP) activity. We therefore investigated the effect of six statins on neointimal formation and MMP activity in human SV organ culture. STUDY DESIGN: Human SV specimens were cultured for 14 days in the presence of six different statins and subsequently processed for measurement of neointimal thickness and MMP activity. The drug concentrations chosen corresponded to the manufacturers' Cmax. RESULTS: The six statins all significantly reduced IH development (P = 0.004) in association with reduced expression of proMMP-2 and 9 (P = 0.03) and reduced activity of activated MMP-2 and 9 (P = 0.03). CONCLUSION: This study suggests that the potential benefit of statins in reducing IH is a class effect and not confined to specific statins. The reduction of IH produced by statins may in part be due to their inhibition of MMPs.