BackgroundCardiovascular disease is the main cause of death in the United States, with smoking being the primary preventable cause of premature death, and thrombosis being the main mechanism of cardiovascular mortality in smokers. Due to the perception that electronic/eācigarettes are āsafer/less harmfulā than conventional cigarettes, their usageāamong a variety of agesāhas increased tremendously during the past decade. Notably, there are limited studies regarding the negative effects of eācigarettes on the cardiovascular system, which is also the subject of significant debate.Methods and ResultsWe employed a passive eāVapeTM vapor inhalation system and developed an inĀ vivo wholeābody eācigarette mouse exposure protocol that mimics realālife human exposure scenarios/conditions and investigated the effects of eācigarettes and clean air on platelet function and thrombogenesis. Our results show that platelets from eācigaretteāexposed mice are hyperactive, with enhanced aggregation, dense and Ī± granule secretion, activation of the Ī±IIbĪ²3 integrin, phosphatidylserine expression, and Akt and ERK activation, when compared with clean airāexposed platelets. Eācigaretteāexposed platelets were also found to be resistant to inhibition by prostacyclin, relative to clean air. Furthermore, the eācigaretteāexposed mice exhibited a shortened thrombosis occlusion and bleeding times.ConclusionsTaken together, our data demonstrate for the first time that eācigarettes alter physiological hemostasis and increase the risk of thrombogenic events. This is attributable, at least in part, to the hyperactive state of platelets. Thus, the negative health consequences of eācigarette exposure should not be underestimated and warrant further investigation.