Background:The seroprevalence of hepatitis C virus (HCV) infection among Canadians is estimated at 0.3% to 0.9%. Of those with chronic HCV infection, 10% to 20% will experience advanced liver disease by 30 years of infection. Targeted screening seems a plausible strategy. We aimed to estimate the health and economic effects of various screening and treatment strategies for chronic HCV infection in Canada. Methods:We used a state-transition model to examine the cost-effectiveness of 4 screening strategies: no screening; screen and treat with pegylated interferon plus ribavarin; screen and treat with pegylated interferon and ribavarinbased direct-acting antiviral agents; and screen and treat with interferon-free direct-acting antivirals. We considered Can adian residents in 2 age groups: 25-64 and 45-64 years of age. We obtained model data from the literature. We predicted deaths related to chronic HCV infection, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. Results:We found that screening and treating would prevent at least 9 HCV-related deaths per 10 000 persons screened over the lifetime of the cohort. Screening was associated with QALY increases of 0.0032 to 0.0095 and cost increases of $124 to $338 per person, which translated to an incremental cost-effectiveness ratio of $34 359 to $44 034 per QALY gained, relative to no screening, depending on age group screened and antiviral therapy received.Interpretation: A selective one-time HCV screening program for people 25-64 or 45-64 years of age in Canada would likely be cost-effective. Identification of silent cases of chronic HCV infection and the offer of treatment when appropriate could extend the lives of Canadians at reasonable cost. Abstract Research E111CMAJ, February 17, 2015, 187(3)