Micro and macrovascular complications occurring during hyperlipidemia are mostly attributed to haemostatic impairment and vascular endothelial dysfunction. Cholesteryl ester transfer protein (CETP) inhibitors have been emerged recently as promising hypocholesterolemic agents to confer protection against lipid-mediated atherosclerosis. Therefore, 10-dehydrogingerdione (DHGD), a novel CETP inhibitor isolated from ginger rhizomes, was selected as a natural product in the present study to illustrate its effect on haemostatic impairment associated with hyperlipidemia as compared to a currently used hypocholesterolemic agent, atorvastatin (ATOR). Rabbits were fed a high cholesterol diet (HCD) and divided into three groups. One group served as control group while the other groups received DHGD or ATOR. Dyslipidemic rabbits showed a significant increase in serum endothelin-1, ischemia modified albumin, plasminogen activator inhibitor-1, prothrombin fragments (1+2) and plasma fibrinogen along with a decrease of nitric oxide level in serum. Daily administration of ATOR or DHGD significantly decreased the aforementioned coagulation and ischemia biomarkers and increased serum nitric oxide. DHGD (natural) results seem to be more remarkable as compared to ATOR (synthetic).