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Electronic cigarettes (e-cigarettes) have become increasingly popular. However, information about the health risks associated with e-cigarette use is sparse. Currently, no published studies examine the effects of chronic e-cigarette exposure on microcirculation or perfusion. Using a rat skin flap model, we examined the toxic microcirculatory effects e-cigarettes may have in comparison with tobacco cigarettes.Fifty-eight rats were randomized to either exposure to room air, tobacco cigarette smoke, medium-nicotine content (1.2%) e-cigarette vapor, or a high-nicotine content (2.4%) e-cigarette vapor. After 4 weeks of exposure, a random pattern, 3 × 9 cm skin flap was elevated on the dorsum of the rats. At 5 weeks, flap survival was evaluated quantitatively, and the rats were euthanized. Plasma was collected for nicotine and cotinine analysis, and flap tissues were harvested for histopathological analysis.Evaluation of the dorsal skin flaps demonstrated significantly increased necrosis in the vapor and tobacco groups. The average necrosis within the groups was as follows: control 19.23%, high-dose vapor 28.61%, medium-dose vapor 35.93%, and tobacco cigarette 30.15%. Although the e-cigarette and tobacco cigarette groups did not differ significantly, each individual group had significantly more necrosis than the control group (P<0.05). These results were corroborated with histopathological analysis of hypoxic tissue.Both the medium-content and high-nicotine content e-cigarette exposure groups had similar amounts of flap necrosis and hypoxia when compared with the tobacco cigarette exposure group. Nicotine-containing e-cigarette vapor is similarly toxic to skin flap survival as tobacco cigarettes.