BACKGROUND: Physiologic studies show that tissue perfusion increases during moderate amounts of tissue compression. This is attributed to sensory nerves initiating a vasodilatory cascade referred to as pressure-induced vasodilation. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies investigating perfusion during pressure exposure longer than 10 minutes. Retrieved studies were assessed using the Office of Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies. Results were pooled with random effects models. The body of evidence was rated using the Office of Health Assessment and Translation approach. RESULTS: Twenty-nine articles were included, of which 19 articles were included in meta-analyses. The evidence indicates that moderate amounts of tissue compression have the capacity to increase perfusion in healthy humans by 46 percent (95 percent CI, 30 to 62 percent). Using the Office of Health Assessment and Translation approach, the authors found a high level of confidence in the body of evidence. Pressure-induced vasodilation blockade was associated with increased pressure ulcer formation. Pressure-induced vasodilation was impaired by neuropathy and by the drugs diclofenac and amiloride. CONCLUSIONS: This systematic review and meta-analysis indicates that healthy humans have the capacity to increase local perfusion in response to mechanical stress resulting from tissue compression. Because pressure-induced vasodilation is mediated by sensory nerves, pressure-induced vasodilation emphasizes the importance of sensory innervation for durable tissue integrity. Pressure-induced vasodilation impairment seems to provide a complementary explanation for the susceptibility of neuropathic tissues to pressure-induced lesions.