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Objectives To evaluate the clinical applicability of autoantibodies (AAbs) measured by ELISA against the angiotensin II type 1 receptor (AT 1R) and endothelin-1 type A receptor (ETAR) in systemic sclerosis (SSc) patients.Methods Serum samples from n=279 SSc patients from the Leiden Systemic Sclerosis cohort, n=42 patients with primary Raynaud’s phenomenon, n=24 patients with rheumatoid arthritis and n=20 healthy controls were tested for anti-AT 1R- and anti-ETAR AAbs. Levels were compared between groups with Mann-Whitney U tests or Kruskal-Wallis tests. Risk ratios and Kaplan-Meier analyses were used to determine associations between AAbs and disease manifestations or all-cause mortality. Analyses were repeated in an independent cohort with n=310 SSc patients from the Radboud University Medical Center.Results AAbs against AT 1R and ETAR could be detected by ELISA in the sera of all groups tested. Levels were slightly higher in the SSc group compared with the pooled non-SSc group (p=0.043). No associations could be found between anti-AT1R AAbs or anti-ETAR AAbs and disease manifestations or all-cause mortality. In the Radboud cohort, patients with diffuse cutaneous SSc (p=0.001) and interstitial lung disease (p=0.007) had higher median anti-ETAR AAb levels. Patients who died during follow-up had lower levels of anti-AT1R- (p=0.005) and anti-ETAR AAbs (p=0.020).Conclusions We confirm positive ELISAs for anti-AT 1R AAbs and anti-ETAR AAbs in the sera of several patient groups and healthy controls. Previously described associations with disease manifestations and all-cause mortality could not be confirmed in our cohorts. Based on the current study, the determination of these AAbs is of limited predictive value in clinical practice.