Abstract: OBJECTIVE To establish an HPLC method for determining the contents of the related substances in clopidogrel bisulfate aspirin tablets. METHODS The chromatographic analysis was performed on Waters XBridge Shield RP₁₈ column(250 mm×4.6 mm, 5 μm) with 0.1% triethylamine(adjusted with phosphoric acid to pH 2.5±0.1) and methanol as mobile phase using gradient elution at a flow rate of 1.0 mL·min⁻¹. The UV detection wavelength was 220 nm. RESULTS Clopidogrel bisulfate, aspirin and relate substances were well separated. The calibration curves were linear in the range of 0.59-178.32 μg·mL^-1 for aspirin impurity C(r=0.999 9), 0.31-12.47 μg·mL^-1 for aspirin impurity D(r=1.000 0), 0.33- 13.21 μg·mL^-1 for aspirin impurity E(r=0.999 8), 0.31-18.49 μg·mL^-1 for aspirin impurity F(r=0.999 7), and 0.76- 30.28 μg·mL^-1 for clopidogrel bisulfate impurity A(r=0.999 9), respectively. The average recoveries of aspirin impurity C, impurity D, impurity E, impurity F and clopidogrel bisulfate impurity A were 97.47%, 102.16%, 102.20%, 103.71% and 104.16% respectively, the RSDs were 5.35%, 1.93%, 1.40%, 4.63% and 2.45% respectively. CONCLUSION The method is simple, accurate, reliable, and can be used for the quality control of the related substances in clopidogrel bisulfate aspirin tablets.