ABSTRACT: BACKGROUND:Initiated in 2016, End Hep C SF is a comprehensive initiative to eliminate hepatitis C (HCV) infection in San Francisco. The introduction of direct-acting antivirals to treat and cure HCV provides an opportunity for elimination. To properly measure progress, an estimate of baseline HCV prevalence, and of the number of people in various subpopulations with active HCV infection, is required to target and measure the impact of interventions. Our analysis was designed to incorporate multiple relevant data sources and estimate HCV burden for the San Francisco population as a whole, including specific key populations at higher risk of infection. METHODS:Our estimates are based on triangulation of data found in case registries, medical records, observational studies, and published literature from 2010 through 2017. We examined subpopulations based on sex, age and/or HCV risk group. When multiple sources of data were available for subpopulation estimates, we calculated a weighted average using inverse variance weighting. Credible ranges (CRs) were derived from 95% confidence intervals of population size and prevalence estimates. RESULTS:We estimate that 21,758 residents of San Francisco are HCV seropositive (CR: 10,274-42,067), representing an overall seroprevalence of 2.5% (CR: 1.2%- 4.9%). Of these, 16,408 are estimated to be viremic (CR: 6,505-37,407), though this estimate includes treated cases; up to 12,257 of these (CR: 2,354-33,256) are people who are untreated and infectious. People who injected drugs in the last year represent 67.9% of viremic HCV infections. CONCLUSIONS:We estimated approximately 7,400 (51%) more HCV seropositive cases than are included in San Francisco's HCV surveillance case registry. Our estimate provides a useful baseline against which the impact of End Hep C SF can be measured.