Background Familial history (FH) of coronary heart disease (CHD) is well-known risk factor of CHD. However, it is not clear whether clinical presentations or prognosis is different, depending on presence of FH. This study explored the impact of FH of CHD on disease presentation and clinical outcome in patients presenting acute myocardial infarction (AMI). Methods 11,635 patients (male 8150 (70%), age 63 짹 13 years) with first-onset AMI during November 2005 to June 2008 in nationwide prospective, multicenter, on-line registry (Korea AMI registry: KAMIR) were analyzed. Clinical characteristics and prognosis (cardiac death and composite major cardiac adverse events (MACEs)) were evaluated. Results The patients with FH of CHD were younger (56 짹 13 vs. 63 짹 13 years), more male (81 vs. 69%) and smokers (69 vs. 56%), and had lower serum glucose (159 짹 79 vs. 171 짹 83 mg/dl) and higher serum creatinine (1.07 짹 0.80 vs. 1.18 짹 1.13 mg/dl), total cholesterol (191 짹 46 vs. 184 짹 44 mg/dl), triglyceride (143 짹 119 vs. 127 짹 105 mg/dl), LDL-cholesterol level (123 짹 40 vs. 117 짹 39 mg/dl, p<0.001 for all). AMI presentation was less severe in patients with FH of CHD (Killip III/IV: 9.1% vs. 13.0 %, p=0.003). However, there was had no significant difference in the extent of CHD between groups (1/2/3 vessel or Lt main: 45/30/24 vs. 43/31/26%, p=0.495). In a Cox regression analysis, after adjusting confounding variables, FH of CHD was related to increased risk of composite MACEs (hazard ratio (HR): 1.32, 95% confidential interval (CI): 1.00-1.73, p=0.047) and cardiac death (HR 1.56, 95% CI: 0.92-2.64, p=0.099), comparable to the presence of peripheral vascular disease. Conclusion AMI patients with FH of CHD are younger, but have unfavorable risk profiles. FH of CHD is an independent prognostic predictor of cardiac events in patients presenting AMI.