Background Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) might benefit from aspirin desensitization (AD) as an alternative treatment to standard care. However, there is conflicting evidence regarding its role in bronchial symptoms and asthma exacerbations. Objective To analyze the clinical effects of AD in terms of lung function, systemic and inhaled steroid use, the frequency of acute asthma exacerbations, and adverse effects in patients with NERD and asthma. Methodology We identified randomized clinical trials (RCTs) from PubMed, EMBASE, SCOPUS, and EBSCO. We also searched the RCT references for additional studies. Studies comparing AD to placebo in patients with a previous history of pulmonary symptoms triggered by ASA or other NSAIDs or with a positive provocation test to ASA were included. Primary results Five studies with 210 participants with NERD were included in this review. The study duration ranged from 3 to 6 months. Overall, the risk of bias across the included RCTs was low. We identified 3 studies evaluating lung function, 2 of which reported a significant improvement in FEV1 in the AD group after 6 months, while the other reported no difference among the treatments. Due to high heterogeneity, we did not pool the results. The remaining primary outcomes were reported only in a single study each, hindering their interpretation. Secondary outcomes revealed reduced symptom and medication scores in patients with AD. Conclusions Due to the small number of studies included in this systematic review, conclusions should be made with caution. AD shows a trend towards improving lung function (FEV1) following 6 months of treatment, although no conclusions can be made regarding the use of corticosteroids or the frequency of acute exacerbations. AD appears to reduce both symptom and medication scores. Additional RCTs are needed to fully assess the efficacy of AD in reducing bronchial symptoms in patients with NERD.