BACKGROUND: There is an ongoing search for novel biomarkers of vascular dysfunction, extent of fibrosis and organ involvement in systemic sclerosis (SSc). OBJECTIVES: We critically appraised the studies investigating the circulating concentrations of endothelin-1 in SSc patients and healthy controls. DESIGN: This was a systematic review with meta-analysis. DATA SOURCES AND METHODS: We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 15 June 2024. We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively. RESULTS: Endothelin-1 concentrations were significantly higher in SSc patients than in controls (26 studies
standardised mean difference, SMD = 0.98, 95% CI 0.73-1.23, CONCLUSION: The results of this systematic review and meta-analysis highlight the potential role of endothelin-1 as a candidate biomarker of SSc. Further research is warranted to determine the utility of measuring endothelin-1 in SSc subgroups with different extent of fibrosis and organ involvement. REGISTRATION: PROSPERO registration number - CRD42024566461.