Background Asthma is an inflammatory disease of the airways with symptoms that vary over time and intensity, sometimes leading to disability or even death. Eosinophilic asthma accounts for 25% of cases of severe asthma. It is mediated by eosinophils regulated by interleukin-5 (IL-5), the target of mepolizumab, which has been recently licensed as an add-on treatment of severe refractory eosinophilic asthma. The aim of this study was to evaluate the effectiveness and safety of mepolizumab in clinical practice. Methods A multicentre, retrospective, and descriptive study covering a year was conducted in a province of Spain with more than 500,000 inhabitants. Every patient prescribed with mepolizumab since its introduction into the hospital was included in the study. Clinical parameters were collected from the pharmacists’ counselling reports from electronic prescription software and electronic patient records. Effectiveness was assessed as a decrease in the exacerbation frequency and/or a reduction in the use of oral corticosteroids (OCS) compared to the previous year. Results A total of 25 patients were studied, but only 23 could be evaluated by the cut-off date. A decrease in the exacerbation frequency was observed in 19 (82.6%) patients, 11 of them without any exacerbation during the treatment. A relative reduction of 87% in the exacerbation rate per year was obtained. A total of 15 patients were on regular OCS – 9 patients (60%) reduced their average dose, whilst 4 (26.7%) patients completely abandoned OCS. Safety was evaluated based on reported adverse effects. Adverse events were observed in 12 patients, the most common being headache, arthralgia, and dizziness/nausea. Conclusion Mepolizumab has been shown to be effective based on the high decrease in the exacerbation frequency and reduced use of OCS. Reported adverse effects were mostly mild and appeared in half of the patients; some of the adverse events had not been previously described in pivotal trials.