Background: Allergic rhinitis (AR), an IgE-mediated inflammatory disease, significantly impacts the quality of life of a considerable proportion of the general population. Omalizumab, a humanized monoclonal antibody against IgE, has been evaluated for both seasonal and perennial AR. We aimed to assess the efficacy and safety of omalizumab in randomized controlled trials (RCTs) in inadequately controlled AR. Methods: We conducted a systematic literature search of RCTs evaluating the safety and efficacy of omalizumab in AR. We synthesized evidence for clinical improvement of AR symptoms, quality of life, reduction of the use of rescue medication, and adverse events. Results: The systematic search returned 289 articles, of which 12 RCTs were eligible for data extraction and meta-analysis. Omalizumab reduced the Daily Nasal Symptom Severity Score (DNSSS) by a summary standardized mean difference of -0.41 points (95% CI: -0.61, -0.22; I2=93.2%), the Daily Ocular Symptom Severity Score (DOSSS) by a summary standardized mean difference of -0.30 points (95% CI: -0.50, -0.01; I2=86.2%), the Rhino-conjunctivitis Quality of Life Questionnaire by a summary standardized mean difference of -0.45 points (95% CI: -0.57, -0.34; I2=0%) and the mean daily consumption of rescue antihistamines by a summary standardized mean difference of -0.21 (95% CI: -0.41, -0.01; I2=85.7%). No statistically significant difference in the occurrence of adverse events was observed between omalizumab and placebo (Relative Risk 1.03; 95% CI: 0.93, 1.14; I2=43.3%). Conclusion: Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with conventional treatment.