To evaluate the efficacy of baricitinib compared to TNF-α Inhibitors and conventional DMARDs (cDMARDs) in patients with RA. Our study included 334 RA patients classified into 3 groups: the first receiving baricitinib, the second receiving TNF-α Inhibitors, and the third receiving cDMARDs. Patients were evaluated at baseline, week 12, and week 24 using TJC, SJC, VAS, DAS28, CDAI, and HAQ-DI. Larsen score was measured at baseline and 24weeks. The response to therapy was assessed at weeks 12 and 24 using ACR 20, ACR 50, and ACR 70 response criteria. Emerging treatment side effects were monitored. Patients receiving baricitinib showed significant improvement regarding all outcome measures at weeks 12 and 24. In addition, baricitinib was comparable to TNF Inhibitors in all outcome measures except the ACR 70 at week 12, which was higher in the baricitinib group. Furthermore, baricitinib group showed significantly better outcome measures and response to therapy in comparison to cDMARDs group. The most common side effects in the baricitinib group were infection, GIT, and CVS complications. The most common side effects in the TNF inhibitors group were infection and skin complications. The cDMARDs had the least side effects, mostly GIT complications. Baricitinib is an effective drug for treating RA refractory to cDMARDs, improving disease activity measures and functional status and reducing the progression of structural joint damage. It has a comparable efficacy and safety profile to TNF Inhibitors. Multicenter studies are recommended to support our results. Key Points • Baricitinib is an effective therapeutic choice for rheumatoid arthritis refractory to cDMARDs. • Patients treated with baricitinib showed improvement in all outcome measures and functional status. • Bricitinib delayed the progression of radiographic joint damage more effectively than cDMARDs. • The efficacy and safety of baricitinib for treating rheumatoid arthritis is comparable to that of TNF inhibitors.