Abstract Objectives A positive family history (PFH) of spondyloarthritis, in particular a PFH of AS or acute anterior uveitis, is associated with HLA-B27 carriership in chronic back pain patients. As it is unknown, the study aimed to investigate if a PFH contributes to diagnosing axial spondyloarthritis (axSpA) once HLA-B27 status is known. Methods In axSpA-suspected patients from the Assessment of SpondyloArthritis international Society (ASAS), DEvenir des Spondyloarthropathies Indifférenciéés Récentes (DESIR) and SPondyloArthritis Caught Early (SPACE) cohorts, logistic regression analyses were performed with HLA-B27 status and PFH according to the ASAS definition (ASAS-PFH) as determinants and clinical axSpA diagnosis as outcome at baseline. Analyses were repeated with a PFH of AS or acute anterior uveitis. Results In total, 1818 patients suspected of axSpA were analysed (ASAS n = 594, DESIR n = 647, and SPACE n = 577). In patients from the ASAS, DESIR and SPACE cohorts, respectively 23%, 39% and 38% had an ASAS-PFH, 52%, 58% and 43% were HLA-B27 positive, and 62%, 47% and 54% were diagnosed with axSpA. HLA-B27 was independently associated with an axSpA diagnosis in each cohort but an ASAS-PFH was not ASAS cohort: HLA-B27 odds ratio (OR): 6.9 (95% CI: 4.7, 10.2), ASAS-PFH OR: 0.9 (95% CI: 0.6, 1.4); DESIR: HLA-B27 OR: 2.1 (95% CI: 1.5, 2.9), ASAS-PFH OR: 1.0 (95% CI 0.7, 1.3); SPACE: HLA-B27 OR: 10.4 (95% CI: 6.9, 15.7), ASAS-PFH OR: 1.0 (95% CI: 0.7, 1.5). Similar negative results were found for PFH of AS and acute anterior uveitis. Conclusion In three independent cohorts with different ethnical backgrounds, ASAS, DESIR and SPACE, a PFH was not associated independently of HLA-B27 with a diagnosis of axSpA. This indicates that in the vast majority of patients presenting with back pain, a PFH does not contribute to the likelihood of an axSpA diagnosis if HLA-B27 status is known.