Objective: Real-world studies on the effectiveness of omalizumab in Egyptian population with asthma are limited. This study aimed to evaluate the real-world effectiveness and safety of omalizumab as an add-on treatment in pediatric and adult patients with severe, persistent allergic asthma in Egypt. Methods: The primary endpoint of this 16-week, prospective, open-label, multicenter, non-interventional study was the reduction in oral corticosteroid (OCS) dose. Secondary endpoints included reduction in exacerbation, improvements in quality of life and global assessment of omalizumab therapy. Results: Of the 59 patients, 53 completed the study. Add-on omalizumab significantly reduced the proportion of patients receiving OCS at Week 16 versus baseline (81.1% at baseline versus 52.8% at Week 16; p < 0.001). A 55% decrease in the total daily prednisolone-equivalent dose of OCS was observed at the end of the study compared to baseline (p < 0.001). No patients reported exacerbations or missed days from work or school after receiving omalizumab for 16 weeks compared to baseline (both p < 0.001). A statistically significant decrease was observed in asthma control questionnaire-5 scores (p < 0.001). Almost all physicians and patients rated omalizumab therapy as 'good,' 'very good' or 'excellent' in tolerability and effectiveness. No new safety signals were observed in the safety analysis of omalizumab as add-on treatment. Conclusions: Outcomes of this real-world study were consistent with previous effectiveness and safety studies of omalizumab. Omalizumab was effective and well tolerated for the management of severe, persistent IgE-mediated asthma in pediatric and adult patients in Egypt.