BACKGROUND: Acute coronary syndromes (ACS) are characterized by abnormal heart-rate variability (HRV) and biomarkers of endothelial damage and thrombosis. HYPOTHESIS: We hypothesized an association between these factors in patients with ACS. METHODS: We studied 99 patients with ACS measuring HRV and plasma markers of endothelial damage/dysfunction (von Willebrand factor, vWF) and thrombosis/hemostasis (soluble P-selectin (s-Psel); CD(40)-ligand (CD(40)-L); D-dimer). HRV and plasma indices were compared to age- and gender-matched controls. Measures were repeated at 4 months in a subset. vWF, s-Psel and D-Dimer levels were raised compared to control. RESULTS: HRV indices were reduced (mean RR, SDNN, SDNNi, RMSSD, Triangular index, LF and HF). There were weak correlations between mean RR and s-Psel (R = - 0.234, p = 0.023) and D-dimer (R = - 0.219, p = 0.041). At 4-month follow-up, significant correlations were between mean RR and CD(40)L (R = - 0.414, p = 0.008) and D-dimer (R = - 0.363, p = 0.012). On multivariate logistic regression analysis statin use (p = 0.046) was the only independent predictor of acute s-Psel levels. Age (p = 0.004) and mean RR interval (p = 0.01) were independent predictors of D-dimer levels at follow-up. CONCLUSIONS: Abnormal HRV is associated with markers of hemostasis and thrombosis in ACS, and present both in the acute and rehabilitation phases.