The relative risk of developing ankylosing spondylitis in HLA-B27-positive patients is more than 100 times that of HLA-B27-negative patients. Therefore, examination of HLA-B27 is helpful in the diagnosis and differential diagnosis of this disease. However, about 80% of B27-positive individuals do not develop ankylosing spondylitis, and about 10% of patients with ankylosing spondylitis are B27-negative. There are also other diseases such as psoriasis and psoriatic arthritis, ulcerative colitis, enteropathic arthritis, Wright’s syndrome, reactive arthritis, and Crohn’s disease that are also positive for the HLA-B27 antigen. Therefore, a positive HLA-B27 does not necessarily mean ankylosing spondylitis, but only that ankylosing spondylitis is more likely, while a B27-negative person cannot be excluded from AS as long as the clinical presentation and imaging meet the diagnostic criteria. In patients with diagnosed ankylosing spondylitis, examination of HLA-B27 can help determine the severity of the disease and its prognosis. Because HLA-B27-positive patients tend to have more severe disease, chronic back pain, sacroiliac arthritis, skin and mucosal lesions, and systemic symptoms such as fever, weight loss and excessive sweating are more common. Recently, it has been found that more than 90% of patients with ankylosing spondylitis presenting with cardiac and ocular involvement are HLA-B27 positive, with HLA-B27 negative patients occurring less frequently. Therefore, some people refer to the cardiac and ocular lesions of ankylosing spondylitis (mainly aortic valve insufficiency, severe cardiac atrioventricular block, and ocular iridocyclitis) as HLA-B27-associated diseases.