Background: Anti-IgE (Omalizumab) is one of the targeted therapies for severe bronchial asthma. Its real-life safety is still under scrutiny. Aim of Study: Was to evaluate the persistent efficacy and safety of Omalizumab as a long-term treatment of severe bron-chial asthma. Patients and Methods: This prospective cohort study eval-uated the long-term safety and efficacy of Omalizumab in 74 patients with severe bronchial asthma attending to the chest de-partment at King Fahd Hospital , Madina; KSA from June 2016 to August 2024. Results: Over a 7-10 year follow-up, Omalizumab demon-strated significant improvements in clinical outcomes. Oral steroid use decreased dramatically, tiotropium bromide use re-duced, and the frequency of acute exacerbations significantly declined. Pulmonary function tests (FEV1, FEV1/FVC, PEFR) showed substantial improvement. While mild side effects like injection site reactions, headache, and nausea were observed primarily in the first year, no serious adverse events such as cancer, anaphylaxis, or myocardial infarction were reported. Conclusion: These findings suggest that long-term Omali-zumab treatment in severe asthma is efficacious and well-toler-ated, with minimal side effects.