Objectives: This study investigated whether perioperative treatment with glucocorticoids (GC) and disease-modifying anti-rheumatic drugs (DMARDs) can improve clinical outcomes and reduce long-term complications for patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA). Methods: Patients were allocated into three groups based on perioperative drug therapy: A. control group (no GC or DMARDs), B. DMARD group (DMARDs given without GC) and C. co-therapy group (DMARDs plus GC). The patients were followed and received questionnaires at the latest follow-up. Baseline characteristics, pre- and post-operative HSS knee score, laboratory parameters, and surgical complications were collected and analyzed. Results: 56 RA patients undergoing 91 TKAs were included in this study. The average follow-up duration was 11.4 years. Patients who received perioperative GC with DMARDs (group C) achieved better HSS score (C:84.04 vs A:78.96 vs B:76.50, p=.008), pain relief (VAS: C: 1.12 vs B: 1.73, p=0.02), higher functional assessment (C:16.17 vs B:13.23, p=0.03) and range of motion (C:132.15 vs A:112.57 vs B:112.51, p<0.001) compared the other treatment groups at time of latest follow-up. Aside from greater post-operative hemoglobin seen in group A compared to group B (P=0.04), no other differences were noted in laboratory tests, blood loss and transfusion, short-term or long-term complications between treatment groups. Conclusions: Perioperative treatment with GC combined DMARDs for RA patients is associated with improved HSS score, better function and range of motion, and reduced postoperative pain in the long term when compared to treatment with DMARDs alone or management without anti-rheumatic medication.