Abstract: Objective To investigate the relationship between serum anti-streptolysin O (ASO) titers and ankylosing spondylitis (AS) disease activity and to analyze the effect of different drug treatments on ASO titers. Methods A retrospective cohort study was conducted to collect serum ASO, ESR, C-reactive protein (CRP), white blood cells (WBC), platelets (PLT), immunoglobulin (Ig) and therapeutic data before and after treatment in AS patients. The relationship between serum ASO titer and ESR, CRP, WBC, PLT and Ig in different stages of AS was analyzed to assess the influence of disease activity and different therapeutic drugs on serum ASO titer.Results Of the 1946 patients enrolled in AS, serum ASO was detected in 926 patients, and 244 patients were found to have elevated ASO titer, with a positive rate of 26.35%. Of these, 43 patients regularly reviewed ASO and related indicators more than twice after treatment. Serum ASO titers were positively correlated with ESR and CRP before treatment (all P<0.05); Serum ASO titer decreased significantly after treatment and the difference was statistically significant (χ²=51.907, P<0.001); The ASO titer was significantly decreased in those who did not use long-acting penicillium and use long-acting penicillus, the differences between the three groups were statistically significant before and after treatment (χ²=11.711, P=0.003; χ²=7.042, P=0.030), and the long-acting penicillin had a more pronounced decrease in the ASO titer than the non-user, the difference between the two groups was statistically significant (F=3.404, P=0.049). Conclusion The serum ASO titer was related to the disease activity before AS treatment, the ASO titer was significantly reduced after treatment, and the ASO titer may reduce more significant with the anti-infective treatment.