Aim To evaluate the relationship between the levels of heparin binding epidermal growth factor(HB-EGF), phosphodiesterase 4D (PDE4D) in serum and acute coronary syndrome(ACS). Methods The protein levels of HB-EGF, PDE4D were measured in serum of 50 patients with ACS (ACS group) and 100 cases normal control (normal control group) by double antibodies sandwich ABC-ELISA method. The relationship between the protein levels and ACS was evaluated by logistic regression analysis. Results After correcting for meaningful factors such as high blood pressure, smoking, TG, TC, LDLC, HDLC and BMI by single factor analysis, it found that the protein level of HB-EGF was associated with whether or not suffering from ACS (OR=4.4,5%CI was 1.2,9.498, P=0.001). The protein level of PDE4D was associated with whether or not suffering from ACS, too (OR=5.9,5%CI was 1.4,4.448, P=0.003). Conclusion The protein levels of HB-EGF, PDE4D in serum was associated with whether or not suffering from ACS. Cases with high protein levels of HB-EGF, PDE4D were at high risk of ACS.