To assess the safety and efficacy of Aspirin desensitization combined with long-term Aspirin therapy in patients with Aspirinexacerbated respiratory disease (AERD). We searched the PubMed, Ovid, Cochrane Library, and Google Scholar databases from inception to October 2018 for articles in English. We only included randomized controlled trials and parallel or cross-over studies in which adults with AERD were randomly assigned to undergo Aspirin desensitization and receive long-term Aspirin therapy or placebo. A total of 869 citations were retrieved, and 6 studies met the criteria for analysis. All studies indicated that nasal symptoms, asthma symptoms, or both improved significantly after Aspirin desensitization. In addition, most studies reported a decline in corticosteroid dosage (oral and inhaled). The 4 studies that reported nasal polyps did not demonstrate a change in nasal polyps with Aspirin therapy compared with placebo. The dropout rates in all studies reviewed ranged from 5.8% to 55.7%, and the most common adverse events were gastrointestinal symptoms. Clearly, Aspirin desensitization and treatment are beneficial for AERD patients, with relief of nasal symptoms, improvement in asthma control, decrease in daily corticosteroid use, and no fatal adverse events. However, the long-term adverse effects of Aspirin desensitization and optimal dosage of Aspirin merit further investigation.