OBJECTIVE: This study sought to examine the prognostic value of heart rate variability (HRV) measurement initiated immediately after emergency department presentation for patients with acute coronary syndrome (ACS). BACKGROUND: Altered HRV has been associated with adverse outcomes in heart disease, but the value of HRV measured during the earliest phases of ACS related to risk of 1-year rehospitalization and death has not been established. METHODS: Twenty-four-hour Holter recordings of 279 patients with ACS were initiated within 45 minutes of emergency department arrival; recordings with >/=18 hours of sinus rhythm were selected for HRV analysis (number [N] =193). Time domain, frequency domain, and nonlinear HRV were examined. Survival analysis was performed. RESULTS: During the 1-year follow-up, 94 patients were event-free, 82 were readmitted, and 17 died. HRV was altered in relation to outcomes. Predictors of rehospitalization included increased normalized high frequency power, decreased normalized low frequency power, and decreased low/high frequency ratio. Normalized high frequency >42 ms(2) predicted rehospitalization while controlling for clinical variables (hazard ratio [HR] =2.3; 95% confidence interval [CI] =1.4-3.8, P=0.001). Variables significantly associated with death included natural logs of total power and ultra low frequency power. A model with ultra low frequency power <8 ms(2) (HR =3.8; 95% CI =1.5-10.1; P=0.007) and troponin >0.3 ng/mL (HR =4.0; 95% CI =1.3-12.1; P=0.016) revealed that each contributed independently in predicting mortality. Nonlinear HRV variables were significant predictors of both outcomes. CONCLUSION: HRV measured close to the ACS onset may assist in risk stratification. HRV cut-points may provide additional, incremental prognostic information to established assessment guidelines, and may be worthy of additional study.