Effect of etanercept and infliximab on bone metabolism indexes in patients with ankylosing spondylitis (AS) were evaluated. The clinical data of 80 patients with ankylosing spondylitis admitted to Affiliated Hospital of Hebei University of Engineering from June 2015 to March 2016 were selected. There were 39 patients treated with Enbrel as Enbrel group and 41 patients treated with Infliximab as Infliximab group. The general data of the two groups of patients were collected and various indexes before and 12 and 24 weeks after treatment were recorded. Adverse reactions of the two groups of patients after treatment were recorded and the clinical efficacy of the drugs was evaluated. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in both groups decreased significantly before and 12 and 24 weeks after treatment (P<0.05), and 24 weeks after treatment showed a downward trend compared with 12 weeks (P<0.05). The β-collagen special sequence (β-CTX) level in the two groups was significantly lower after treatment than before (P<0.0001). The adverse reaction rate of Infliximab group (21.95%) was higher than that of Enbrel group (5.13%) (P>0.05). The morning stiffness time, BASDAI and BASFI indexes of the two groups of patients after treatment were significantly lower than those before treatment (P<0.0001). Schober test was significantly higher than that before treatment (P<0.0001); BASDAI in Infliximab group was lower than that in etanercept group (P<0.05). Both etanercept and infliximab have good therapeutic effects on AS, which can reduce the bone metabolism level of β-CTX in AS patients and effectively improve the symptoms of affected medullary joints. The short-term efficacy of the two groups of patients is similar, but the incidence of adverse reactions of etanercept is slightly lower than that of infliximab.