Early treatment of acute hepatitis C virus (HCV) infections reflects a new clinical paradigm and a significant option to reduce the socioeconomic burden of HCV. Therefore, this approach seems suitable as a new strategy to face HCV and prevent end stage liver diseases and premature deaths due to progressed chronic HCV-infections. The main limitation of this approach is that the majority of acute infections show an asymptomatic course and do thus not present to the health-care settings. Screening for HCV has already been extensively studied in the literature. This paper offers further insights in screening for HCV using cost effectiveness analysis for the impact of screening in two cohorts: Injecting Drug Users (IDUs) and Individuals With Surgery (IWSs). The setting of the cost effectiveness simulation is the Veneto Region in the North-east of Italy. Using a Markov model of the natural history of HCV infection we derive costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness related to screening vs. no-screening strategies. In the IDUs cohort, the screening strategy can result in a substantial difference in premature deaths and dominates (less costs better outcomes) the no-screening one. The overall outcomes of the screening strategy are mostly affected by the prevalence of HCV and of genotypes that are more relatively more difficult to treat (above 10% of prevalence for its cost effectiveness). The number of premature deaths prevented in the IWSs cohort is lower and there seems to be an unacceptable incremental cost per QALY gained, which may be unsustainable for society.