Background Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) play an important role in the development of plaque rupture, which leads to acute coronary syndrome (ACS). Objective We evaluated whether functional polymorophisms in the promoter regions of MCP-1 (A-2518G polymorphism) and MMP-9 (C-1562T polymorphism) are predictive factors for the development of acute coronary syndrome. Methods A polymerase chain reaction followed by restriction fragment length polymorphism analysis was performed in 206 consecutive patients with acute coronary syndrome and 173 control participants. Results No association between MCP-1 A-2518G polymorphism and susceptibility to acute coronary syndrome was found. However, there was a significantly higher incidence of the MMP-9 C-1562T polymorphism in the ACS group than in the control group (27.6% compared with 17.9%, P=0.04). Multiple logistic regression analysis using risk factors and MMP-9 C-1562T polymorphism showed that the MMP-9 polymorphism was an important predictive factor for acute coronary syndrome (odds ratio 1.67, 95% confidence interval 1.02-2.74, P=0.04). Conclusion Our results suggest that the functional genetic polymorphism of MMP-9 gene might influence MMP-9 gene promoter activity and have a significant role in the process of plaque rupture.