Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder. One of the primary pro-inflammatory cytokines that involved in joint damage is tumor necrosis factor alpha (TNFα). RA is treated using variety of disease modifying anti-rheumatic drugs (DMARDs). The conventional-synthetic disease modifying anti-rheumatic drugs (cs-DMARDs) are corner stone in the treatment of RA patients, however they have limited efficacy in induction of remission. Objective: This study aims to assess the hematological impact of biological therapy in Rheumatoid arthritis patients in comparison to conventional synthetic disease modifying anti rheumatic drugs. Patients and methods: On the other hand, the biological therapies are potent and strong, highly targeted therapy that successfully induce remission. This study compares the hematological effects of biological therapy and conventional synthetic disease-modifying anti-rheumatic medications in patients with rheumatoid arthritis. Results: Our results showed that patients on biological therapy had lower total leucocytic and neutrophils count with higher lymphocyte count. As well as, they showed statistically highly significant lower RDW with statistically significant higher hematocrit value, Hb concentration, RBCs count and MCV. Finally, we found that there was a statistically significant correlation between the duration of biological therapy and the RDW and MPV, and a highly statistically significant correlation with the values of Hb concentration, total platelet count and their related ratios. Conclusion: Biological therapy had obvious effects on hematological parameters, and these effects were related partially to the potent nature of these group of drugs and partially related to the nature of each therapeutic agent. Additionally, these hematological effects were in strong correlation with the duration of biological use.