BACKGROUND: Endothelial dysfunction is associated with cardiovascular disease and cardiac events. Numerous studies demonstrate that a reduction in physical activity/exercise levels are associated with poor endothelial function. Yet, these studies use a plethora of models to mimic reduced activity levels which may have widely different results on endothelial function. It is pertinent to collectively review these articles to provide a comprehensive understanding of the impact of reduced activity on vascular health, as endothelial function is one of many factors that influences vascular tone. OBJECTIVE: The purpose of this systematic review is to examine and synthesize the current literature regarding the effects of acutely (≤ ~ 2 months) reducing physical activity on endothelial function. METHODS: This systematic review contains a search of two databases (PubMed, Web of Science) conducted by two reviewers. After screening and review, the search yielded 20 studies that were appraised and reviewed. RESULTS: Articles were separated into four categories based on the type of inactivity intervention: reduction in daily physical activity interventions, detraining (removal of exercise) interventions, bed rest interventions, and immobilization interventions. Acute physical inactivity interventions were largely shown to reduce upper and lower limb artery flow-mediated dilation and lower limb microvascular function. CONCLUSION: The results indicate that those studies with increased time spent in inactivity, as well as increased severity of inactivity, were more likely to have negative endothelial function outcomes. Future research should examine differences in the severity of physical inactivity interventions regarding endothelial function.