Thrombosis is a major cause of morbidity and mortality worldwide, with acomplex and multifactorial pathogenesis. Recent studies have shown thatSIRT1, a member of the sirtuin family of NAD + -dependent deacetylases,plays a crucial role in regulating thrombosis, modulating key pathwaysincluding endothelial activation, platelet aggregation, and coagulation.Furthermore, SIRT1 displays anti-inflammatory activity both in vitro, in vivo andin clinical studies, particularly via the reduction of oxidative stress. On these bases,several studies have investigated the therapeutic potential of targeting SIRT1 forthe prevention of thrombosis. This review provides a comprehensive and criticaloverview of the main preclinical and clinical studies and of the currentunderstanding of the role of SIRT1 in thrombosis.