The present invention relates to novel O-acyloxime derivatives, a preparation method thereof and a pharmaceutical composition comprising the same for prevention and treatment of cardiovascular disease. The O-acyloxime derivatives according to the present invention may valuably be used for prevention and treatment of cardiovascular diseases such as hyperlipidemia, coronary arterial heart disease, atherosclerosis, and myocardial infarction caused by Lp-PLA.sub.2, because they have excellent inhibitory effect of Lp-PLA.sub.2.