Undifferentiated spondyloarthritis (USpA) is a major member of the spondyloarthritis family. Ankylosing spondylitis (AS), the prototype of the family, is a largely genetic disease, with human leukocyte antigens (HLA)-B27 being the essential gene. Other genes in the HLA region have also been implicated. The purpose of this study was to identify the alleles of the HLA-A, -B, -C, -DR, and -DQ, which are present at higher frequencies in USpA patients compared with an ethnically matched control population.Sixty-three Taiwanese patients with USpA were compared with 75 matched healthy controls. HLA typing was performed by polymerase chain reaction-sequence specific oligo-nucleotide genotyping.The frequencies of HLA-B27, -B60, -C3, and -DR12 were strikingly higher in USpA patients compared with healthy subjects, with odds ratios of 75.4, 14.0, 9.6, and 7.0, respectively. When USpA patients with axial involvement were compared with those with peripheral arthritis, the following were more marginally frequent in those with axial involvement: HLA-B27 and -DR12 (odds ratios, 4.0 and 4.0, respectively). There was no association of HLA typing with other variables, including enthesitis, uveitis, erythrocyte sedimentation rate, and serum C-reactive protein. Interestingly, in 12 HLA-B27-negative USpA patients, HLA-B60, -C3, and -DR12 were more frequent compared with controls (odds ratios, 35, 16.2, and 8.1, respectively).Similar to AS, USpA is also linked to HLA-B27. A linkage to other HLA alleles observed here, even in our HLA-B27-negative USpA patients, strongly suggests that USpA in general is a genetic disease.