BACKGROUND Rituximab (RTX) is a chimeric therapeutic monoclonal antibody that targets the CD20 molecule on B lymphocytes. RTX is approved for the treatment of rheumatoid arthritis (RA) in patients who do not respond to disease-modifying anti-rheumatic drugs (DMARDs) or other biologics. The purpose of this retrospective study was to report our experience with RTX treatment at a single center in Saudi Arabia between 2015 and 2022 in 52 patients with RA. MATERIAL AND METHODS This retrospective cohort study at King Khalid University Hospital in Riyadh examined 52 patients with RA who received RTX from April 2015 to October 2022. Data were collected from electronic health records, including patient demographics, disease activity, and treatment details. The primary outcome was prednisolone tapering, with secondary outcomes including adverse reactions and disease activity. Statistical analysis was conducted using SPSS. RESULTS Out of 678 screened patients, 52 (7.7%) were recruited. Of these, 44 (84.6%) were female, with a mean disease duration of 28±7 years and a mean age of 57.1±11 years. Prednisolone was used by 22 patients (42.31%) at RTX initiation, with a mean dose of 10.45±10.25 mg. After RTX, the dose significantly dropped to 3.41±5.54 mg (P<0.001). Older patients, those from outside Riyadh, and those with fewer prior DMARDs were more likely to taper off without full dose reinstatement. CONCLUSIONS This retrospective study supports the findings from other studies and current clinical guidelines that recommend rituximab in patients with rheumatoid arthritis, highlighting the importance of patient monitoring during treatment. Multicenter studies are required to determine the economic impact of tapering biological drugs.