Aim: Immune checkpoint inhibitors revolutionized the treatment of non-small-cell lung cancer, although their costs are a limitation. Methods: The number of patients with non-small-cell lung cancer eligible for immunotherapy was estimated using local epidemiology data. We extracted survival data from RCTs to estimate the life-years saved in a 5-year time horizon. All costs were in local prices converted to US dollars. Results: In the first-line, the budget impact of pembrolizumab decreased by 35% through risk-sharing. In the second-line, patient selection by programmed-death receptor ligand 1 expression decreased the budgetary impact by 45%, and improved cost–effectiveness. Immunotherapy was more cost-effective in the first-line. Conclusion: Given current pricing, immune checkpoint inhibitors are cost-prohibitive in the majority of South American health services. Nevertheless, several strategies should improve access to immunotherapy.