Selective sodium–glucose co-transporter 2 (SGLT-2) inhibition by empagliflozin improves clinical outcomes in patients with atherosclerotic cardiovascular disease (ASCVD) independently of its glucose lowering effects. Yet, its mechanism of action remains largely undetermined. In this original investigation members of the CMC reveal that SGLT-2 inhibition by empagliflozin does not impact experimental arterial thrombus formation, neither under baseline conditions nor during sustained low-grade inflammation, and has no impact on proxies of thrombotic/fibrinolytic activity in patients with ASCVD. The authors conclude that the beneficial pleiotropic effects of empagliflozin are likely independent of pathways mediating arterial thrombosis. Full study results now available at https://doi.org/10.1093/cvr/cvac126.