Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction. Prostacyclin synthase (PGIS), a catalyst of PGI2 synthesis from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PGIS gene is localized to 20q13.11-13, and a candidate gene for cardiovascular disease. We discovered mutations and polymorphisms in this gene and reported that they were associated with essential hypertension, myocardial infarction and cerebral infarction. These results suggest that PGI2 function depends on the different alleles of the PGIS gene and that they may influence the risk of cardiovascular diseases. Thus, individualized management strategies, such as administration of PGI2 analog, could be selected for variants of this gene to help prevent the development of cardiovascular diseases.