Background and purpose The EndoFLIP® system is a method of delineating impedance and was first designed to investigate the characteristics of the esophago‐gastric junction. In the last decade, its use was widened to investigate other sphincteric and non‐sphincteric systems of the gastrointestinal tract. The objective of the present systematic review was to summarize the available data in literature on the use of the EndoFLIP® system in the gastrointestinal tract, including sphincteric and non‐sphincteric regions. We performed a systematic review in accordance with recommendations for systematic review using PRISMA guidelines without date restriction, until June 2020, using MEDLINE‐PubMed, Cochrane Library, and Google Scholar databases. Only articles written in English were included in the present review. Five hundred and six unique citations were identified from all database combined. Of those, 95 met the inclusion criteria. There was a lack of standardization among studies in terms of anesthetic drugs use, probe placement, and inflation protocol. In most cases, only small cohorts of patients were included. Most studies investigated the EGJ, with a potential use of the EndoFLIP® to identify a subgroup of patients with achalasia and for intraoperative assessment of treatment efficacy in achalasia. However, the use of EndoFLIP® in the esophageal body (esophageal panometry), other esophageal diseases (gastro‐esophageal reflux disease, eosinophilic esophagitis), and other sphincter regions (anal canal, pylorus) will need further confirmatory studies. The EndoFLIP® system provides detailed geometric data of the gastrointestinal lumen but further works are needed to determine its use in clinical practice. XXXX