BACKGROUND The aim of this study was to investigate the effects of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on patients with ankylosing spondylitis (AS) using real-world data, and to analyze patients' choices of csDMARDs and reasons for discontinuation. MATERIAL AND METHODS This observational study included 320 patients satisfying the modified New York criteria for AS. Patients were grouped according to medication: Group 1: 122 patients receiving non-steroidal anti-inflammatory drug (NSAID) monotherapy; Group 2: 198 patients receiving csDMARDs and NSAIDs. Patients were followed for 18 months at 6-month intervals. The change in AS Disease Activity Score and C-reactive protein (ASDAS-CRP) at each visit was the primary outcome. Secondary outcomes were based on validated disease activity questionnaires, clinical assessment, and acute-phase biomarkers (CRP and erythrocyte sedimentation rate [ESR]). Inter-group relationships were assessed across the 18-month follow-up period using generalized additive mixed models. RESULTS Sulfasalazine and thalidomide were the most commonly used csDMARDs, with cumulative use times of 8.9±4.1 months and 9.1±4.7 months, respectively. In Group 2, 56 patients discontinued or switched csDMARDs during the follow-up period, with lack of efficacy being the primary reason. The ASDAS-CRP was found to decrease significantly in both groups; however, improvements in many parameters (including ASDAS-CRP, disease activity questionnaires and ESR) were greater in Group 2. CONCLUSIONS Use of csDMARDs can improve disease activity in terms of ASDAS-CRP. The addition of csDMARDs may provide increased benefits compared with NSAID monotherapy, particularly in the reduction of AS disease activity, in the Chinese population.