Objective : Objective: To assess and compare the impact of biologic agents used to treat rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), and other autoimmune diseases on different domains of health-related quality of life— physical, psychological, mental, and social aspects of well-being that are influenced by disease. Design : A prospective observational cohort study assessed the effect of biologic therapy on HRQOL for patients in Alexandria Main University Hospital, Alexandria, Egypt. It was conducted between December 2020 and August 2021. The drugs tested were Adalimumab-atto (Amjevita), a monoclonal anti-tumor necrosis factor alpha; Secukinumab (cosentyx), a monoclonal antibody to interleukin-17A; and Etanercept (Enbrel), a tumor necrosis factor (TNF) blocker. Adalimumab (humira) tumor necrosis factor (TNF) blockers, Infliximab (remicade) tumor necrosis factor (TNF)-alpha blockers, and Golimumab (simponi) tumor necrosis factor (TNF) inhibitors. Patient-reported outcomes on 70 participants were done using the validated Arabic version of the SF-36 questionnaire in the form of an oral interview to assess physical, social functioning, role limitations, emotional state, and general health. Results: Patient outcomes for biologics on the 8 domains of the Short-Form questionnaire SF-36 are expressed by mean +/- SD; for physical functioning is 49.03+/-28.31 and median is 45, for role limitation due to physical health is 41.07 ± 39.02 and median is 25, for role limitation due to emotional problems is 51.43 ± 42.73 and median is 66.7, for energy/fatigue is 41.43 ± 16.94 and median is 45, for emotional wellbeing is 48.17 ± 18.20 and median is 52, for social functioning is 55.16 ± 24.86 and median is 62.5, for pain is 55.93 ± 21.56 and median is 55, for general health is 38.74 ± 13.64 and median is 40, for health change is 68.93 ± 25.34 and median is 75. Conclusion: Infliximab showed significantly better results than Adalimumab and Etanercept regarding physical functioning. Infliximab also established a better outcome in role limitation due to physical health compared to Adalimumab-atto and Adalimumab. Also, Infliximab was significantly better than Adalimumab regarding energy and fatigue. Adalimumab-atto demonstrated a significantly better effect on energy and fatigue than its reference product, Adalimumab. In rheumatoid arthritis cases, Adalimumab-atto had more favorable outcomes than its reference product, Adalimumab, in terms of energy, fatigue, and emotional well-being. While Etanercept demonstrated better pain management than Adalimumab..