Objective: Mepolizumab, an anti-interleukin 5 humanized monoclonal antibody, which is listed among the treatment options in the Global Initiative for Asthma 2020, is recommended as a step 5 therapy option for patients with uncontrolled severe eosinophilic asthma. Real-life data on adverse drug reactions of mepolizumab are limited. We aimed to analyze the safety profile of mepolizumab retrospectively among patients who were treated with mepolizumab with the diagnosis of eosinophilic severe asthma. Materials and Methods: Severe eosinophilic asthma patients from two different centers who were treated with mepolizumab between June 2018 and July 2020 were analyzed retrospectively. The data of the mepolizumab-related adverse event forms, which were filled out at each visit, were retrospectively evaluated. Results: Eighty three patients were included in the study. The most commonly reported adverse events which could be related to mepolizumab were myalgia/arthralgia, headache, and local injection site reactions. Nevertheless, none of these required the discontinuation of the drug. Mepolizumab-related adverse events that required discontinuation of mepolizumab treatment were observed in two (2.4%) cases but their association with the drug could not be clearly defined. Anaphylaxis or herpes infection was not detected in any of the cases. Conclusion: These outcomes reveal that mepolizumab is a well-tolerated drug in real-life. However, further large-scale real-life studies with long-term follow-up are still needed.