OBJECTIVES: Around 185,000 and 600,000 people are at present chronically infected by HCV in France and Romania, respectively. HCV is the leading cause of chronic liver disease and constitutes a significant burden in terms of health and costs for both the individual and society. The direct-acting antivirals have revolutionized the treatment landscape of HCV and raised the possibility of HCV elimination. The objective of the study was to assess the present and future burden of HCV in France and Romania. METHODS: To estimate the future burden of HCV in France and Romania, a population based disease burden model was developed to simulate fibrosis progression in the prevalent and incident HCV-population. The model takes into account diagnosis status, screening and treatment efficacy of current standard of care. The model was populated with published data. Under the assumption that DAAs is used, today’s treatment levels remain constant, and no screening takes place, health outcomes, mortality, direct and indirect costs related to HCV in France and Romania was estimated between 2015 and 2040. RESULTS: In France, the number of diagnosed patients will decrease to around 10,000 individuals by 2025. In addition, annual economic burden of HCV will be around 80% lower compared with today. However, around 35,000 will remain undiagnosed and at risk of developing decompensated cirrhosis and hepatocellular carcinoma. In Romania, morbidity and associated costs will continue to increase under current treatment levels. Annual mortality in Romania due to HCV is estimated to increase by > 70% between 2015 and 2040. CONCLUSIONS: Under current standard of care, France will reduce the current burden of HCV substantially by 2025 but must couple this with screening in order to be able to achieve complete elimination. On the contrary, Romania faces a future with significantly higher burden of HCV unless treatment levels are increased.