Purpose The aim was to conduct a systematic literature review and meta-anaylsis to analyze the diagnostic accuracy of the external rotation stress test (ERST) for syndesmotic injuries. Methods The systematic review was conducted according to the PRISMA-P guidelines (Prospero ID: CRD42021282457). Four common databases were searched from inception to September 29, 2021. Eligible were any studies facilitating the ERST under fluoroscopy in a defined state of syndesmotic instability. Syndesmotic ligament-specific rupture must have been proven by MRI, arthroscopy, or controlled dissection (cadaver study). Two reviewers independently conducted each step of the systematic literature review. The risk of bias was assessed by the Quality Appraisal for Cadaveric Studies Score scale. The data analysis was performed qualitatively and quantitatively. Results Eight studies were eligible for a qualitative analysis, and six studies were eligible for a quantitative analysis. All studies included were cadaver studies. The qualitative analysis comprised 94 specimens and revealed considerable heterogeneity. Six studies allowed for a quantitative analysis of the tibiofibular clear space (TFCS) and five studies for the medial clear space (MCS) during the ERST. The quantitative analysis of the TFCS revealed no significant differences between intact and any stage of syndesmotic injury. The MCS was able to differentiate between intact and 2-ligament- (Z = 2.04, P = 0.02), 3-ligament- (Z = 3.2, P = 0.001), and 3-ligament + deltoid ruptures (Z = 3.35, P < 0.001). Conclusion The ERST is the only noninvasive test to assess syndesmotic instability and can be conducted bilaterally. The uninjured contralateral side can serve as a baseline reference. Based on the conducted quantitative analysis, the MCS seems to be able to differentiate between stable (intact/1-ligament) and unstable (2-ligament/3-ligament) lesions.