Background: Assessment of clinical outcomes in the real-world corroborates findings from randomized controlled trials (RCTs). Objective: This meta-analysis evaluated real-world data of omalizumab on treatment response, lung function, exacerbations, oral corticosteroid (OCS) use, patient-reported outcomes (PROs), health care resource utilization (HCRU), and school/work absenteeism at 4, 6, and 12 months after treatment. Methods: Observational studies in patients with severe allergic asthma (≥6 years) treated with omalizumab for ≥16 weeks, published from January 2005 to October 2018, were retrieved from PubMed, Embase, and Cochrane. A random-effects model was used to assess heterogeneity. Results: In total, 86 publications were included. Global evaluation of treatment effectiveness (GETE) was good/excellent in 77% patients at 16 weeks (risk difference: 0.77; 95% confidence interval [CI]: 0.70-0.84; I2 = 96%) and in 82% patients at 12 months (0.82, 0.73-0.91; 97%). The mean improvement in forced expiratory volume in 1 second was 160, 220, and 250 mL at 16 weeks, 6 months, and 12 months, respectively. There was a decrease in Asthma Control Questionnaire score at 16 weeks (-1.14), 6 months (-1.56), and 12 months (-1.13) after omalizumab therapy. Omalizumab significantly reduced annualized rate of severe exacerbations (risk ratio [RR]: 0.41, 95% CI: 0.30-0.56; I2 = 96%), proportion of patients receiving OCS (RR: 0.59, 95% CI: 0.47-0.75; I2 = 96%), and number of unscheduled physician visits (mean difference: -2.34, 95% CI: -3.54 to -1.13; I2 = 98%) at 12 months versus baseline. Conclusion: The consistent improvements in GETE, lung function, and PROs, and reductions in asthma exacerbations, OCS use, and HCRU with add-on omalizumab in real-life confirm and complement the efficacy data of RCTs.