Background: High density lipoprotein cholesterol (HDL) has been shown to have specific anti-inflammatory activity. Although HDL is used in combination with other markers, the significance of HDL alone in patients with ST-segment elevation myocardial infarction (STEMI) is unclear. The aim of this study was to evaluate the relationship between the HDL and outcome after STEMI. Methods: A total of 1917 patients (64.2짹12.7 years, male 72.3 %) with STEMI who were registered in Korea Acute Myocardial Infarction Registry from Nov. 2005 to Dec. 2006 had fasting lipid panels collected. One-year follow-up (F-U) was completed in 1699 patients. The patients were divided into two groups (group I: ��� HDL 42 mg/dL, n=1106; group II: HDL < 42 mg/dL, n=819). Isolated HDL as well as the ratio triglyceride (TG)/HDL and low density lipoprotein cholesterol (LDL)/HDL ratio were analyzed as predictor of in-hospital adverse events (IHAEs) and long-term clinical outcome. Results: Group I had lower BMI and level of hsCRP than in the group II (p=0.002, p=0.005, respectively). Group I had higher level of total cholesterol, LDL and creatine-kinase MB than in the group II (p<0.001, p<0.001, p=0.031, respectively). HDL was negatively correlated with body mass index and high sensitivity C-reactive protein (r=-0.196, p=0.001; r=-0.221, p<0.001, respectively). Group I had significantly lower IHAEs than Group II (20.3% vs. 28.4%, p<0.001). One-year F-U major adverse cardiac events occurred less frequently in group I compared with the group II (13.8% vs. 17.5%, p=0.040). Multivariate logistic regression analysis showed that HDL < 42 mg/dL was the independent predictor of IHAEs and long-tern clinical outcome [Hazard ratio (HR): 1.955, 95% CI 1.531-2.496, p<0.001, and HR: 1.581, 95% CI 1.176-2.126, p=0.002, respectively]. Both TG/HDL and LDL/HDL ratio were significant predictor of IHAEs in patients with STEMI. MACE-free survival rate was different between the groups at 1- year F-U (p=0.043). Conclusion: HDL was the independent predictor of IHAEs and long-term clinical outcome in the STEMI. Strategies to increase HDL levels may play a pivotal role for overall cardiac protection in this population.