Background: Remission of asthma can occur as part of the natural history of the disease; however, the use of biologics can result in disease remission in some patients. Objective: In this post hoc analysis of the RELIght study, we aimed to evaluate clinical remission in real life among patients treated with mepolizumab, to detect possible differences between "remitters" and "nonremitters," and to evaluate possible predictors of remission. Methods: Clinical remission was defined as the absence of asthma exacerbations, discontinuation of oral corticosteroids (OCS), achievement of asthma control (Asthma Control Test [ACT] ≥ 20), and stable or improved lung function. Results: A total of 146 patients were evaluated; remission was achieved in 40 (27.4%) and 29 (22%) after 12 and 24 months, respectively. At 12 months, the patients in remission had a better baseline ACT score (17.0 [14.0-19.0] versus 15.0 [12.0-17.0]; p = 0.027), were more rarely using OCS (35% versus 62.2%; p = 0.004), and required a lower baseline dose of OCS (5.0 mg/day [5.0-10.0 mg/day] versus 10.0 mg/day [5.0-15.0 mg/day]; p = 0.042) at baseline, whereas, at 24 months, they less frequently carried a baseline diagnosis of gastroesophageal reflux disease (GERD) (10.3% versus 32%; p = 0.031) and used lower doses of OCS at baseline (5.0 [1.0-5.0] versus 10.0 [5.0-15.0]; p = ≤0.001) versus nonremitters; 52.5% of patients had sustained remission, whereas 42.5% experienced relapse. These patients more frequently had GERD versus patients with sustained remission (52.9% versus 4.8%; p = 0.002). Finally, regression analysis has shown that GERD was the only predictor of relapse. Conclusion: Remitters had better asthma control and needed lower doses or no maintenance OCS at baseline, whereas GERD seems to be an important factor that affects remission and relapse.Clinical trial NCT04084613, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinical trials.gov">www.clinical trials.gov</ext-link>.