BACKGROUND: Adverse events (AEs) related to medical treatments in non-small cell lung cancer (NSCLC) are frequent and need an appropriate costing in health economic models. Nevertheless, data on costs associated with AEs in NSCLC are scarce, particularly since the development of immunotherapy with specific immune-related AEs. OBJECTIVE: To estimate the costs of grades 3 and 4 AEs related to NSCLC treatments including immunotherapy in France. METHODS: Grades 3 and 4 AEs related to treatment and reported in at least 1% of patients in Phase III clinical trials for erlotinib, ramucirumab plus docetaxel, docetaxel, pemetrexed plus carboplatin plus bevacizumab, platinum-based chemotherapies, nivolumab and pembrolizumab were identified. When no cost evaluation was reported in literature, estimates on standard treatments and medical resource use for each AE were obtained thanks to an expert panel. Total cost per AE was calculated from a French national health insurance perspective and updated in 2017 Euros. Hospital stay costs were estimated based on public and private weighted tariffs and data from the French Medical Information System (Programme de Medicalisation des Systemes d’Information). Costs of tests, consultations and treatments were calculated based on national reimbursement tariffs. RESULTS: Overall, costs of grades 3 and 4 AEs related to treatment ranged from euro46 per event to euro7,742 per year. Fourteen out of 24 AEs identified had a mean estimated cost over euro2,000. The highest mean costs were related to type 1 diabetes (euro7,742 per year) followed by pneumonitis (euro5,786 per event), anemia (euro5,752 per event), dehydration (euro5,207 per event) and anorexia (euro4,349 per event). Costs were mostly driven by hospitalization costs. CONCLUSION: Among the AEs identified, a majority appeared to have an important economic impact, with a management cost of at least euro2,000 per event mainly driven by hospitalization costs. This study may be of interest for economic evaluations of new interventions in NSCLC.