OBJECTIVES: First-line EGFR-TKIs has become established in EGFR mutation–positive NSCLC. According to large scale meta-analysis, erlotinib and afatinib showed a non-significant difference in efficacy; however, the incidence and severity of EGFR-TKI–related adverse events (AE) was lower with erlotinib. These safety differences may be related to the mechanisms of action (e.g. reversible versus irreversible inhibition). This study aims to compare the AE costs associated with both drugs, from the perspective of the Spanish National Health System (NHS). METHODS: The frequency of AE was obtained from a recently published meta-analysis using log-linear mixed-effects models. In Spain, the daily cost of both treatments is the same, therefore, only the AE costs were considered. The resources use in the AE management were estimated by a Spanish oncologist’s panel and from previous studies conducted in Spain. Monte-Carlo simulation was chosen as it allows simulating the effect of changes in different parameters obtained from clinical studies and other sources to describe real-life distributions. Parameters used in the simulation were the AE rates and AE management costs. RESULTS: