Background: Coronary artery disease (CAD) is one of the leading causes of death worldwide. Clopidogrel, antiplatelet drug, has been widely used for management of CAD. Arylesterase, the activity of Paraoxonase-1 (PON-1), is mainly contributed in the biotransformation of clopidogrel to its active thiol form. The purpose of this study was to investigate the effect of receiving clopidogrel drug on the arylesterase activities in CAD patients. The effect of receiving clopidogrel drug on the antioxidant activity of arylesterase was also monitored by determination of malondialdehyde (MDA) level. Methods: One hundred CAD patients, who were followed-up for 5 days after reciving clopidogrel, and 50 healthy volunteers were included in our study. The activities of arylesterase using two (phenyl acetate and p-nitrophenyl acetate) substrates, lipid profile, MDA, and total protein concentration (Tp) were determined spectrophotometrically. Results: PON-1 arylesterase activities, HDL-C, and Tp were significantly decreased (P<0.0001) in patients with CAD before receiving clopidogrel drug (CAD-pre-Clp) compared to baseline (non-CAD) and the levels of these parameters were returned to baseline (P>0.05) after 5 days of receiving clopidogrel (CAD-post-Clp).