Background. Infliximab (IFX) biosimilar was the first biosimilar approved in Jordan in 2014, with limited evidence of its safety and effectiveness from the Middle East and North Africa (MENA) region. Thus, this study aimed to evaluate the safety and effectiveness of IFX biosimilar in active rheumatoid arthritis (RA) patients over 34 weeks by investigating (1) the adverse events (AEs), serious adverse events (SAEs), and therapy discontinuation and (2) the score changes of the 28-Joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ-DI). Methods. This multicenter prospective cohort study collected clinical parameters within hospital settings every four weeks. The numbers and percentages of observed AEs and SAEs were informed. The DAS28 utilizing Erythrocyte Sedimentation Rate (ESR), HAQ-DI, and ESR were reported at baseline and 14th and 30th weeks; thus, they were reported as means (SD). Results. A total of 22 RA patients were enrolled and initiated IFX biosimilar, of which nine (41.0%) discontinued the study, but their data were analyzed up to the point of withdrawal. A total of 35 AEs were reported in 14 patients, including two (5.7%) SAEs. None of the participants discontinued treatment due to AEs. The mean (SD) score of DAS28-ESR significantly decreased from 6.55 (1.16) at baseline to 4.59 (1.45) at week 14 ( p < 0.0001 ) and to 4.77 (1.09) at week 30 ( p < 0.0001 ). Similarly, the mean (SD) HAQ-DI score significantly decreased from 0.95 (0.74) at baseline to 0.48 (0.62) at week 14 ( p = 0.008 ) and to 0.71 (0.78) at week 30 ( p = 0.483 ). The mean (SD) value of ESR decreased from 58.75 (26.94) at baseline to 47.92 (33.89) at week 14 ( p = 0.082 ) and to 39.83 (17.38) at week 30 ( p = 0.005 ). Conclusion. IFX biosimilar demonstrated safety and effectiveness in managing RA patients bringing real-world clinical support for biosimilars’ role in rheumatology.