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This study examined whether future COVID-19 vaccine acceptance differed based on an experimental manipulation of the vaccine safety and effectiveness profile. Data come from the Detroit Metro Area Community Study, a population-based study conducted July 15–20, 2020. Participants were asked whether they would get a new COVID-19 vaccine after being randomly assigned information about the vaccine’s effectiveness (50% or 95%) and chance of fever (5% or 20%). Among 1,117 Detroiters, 51.3% would accept a COVID-19 vaccine that is 50% effective and 77.1% would accept a vaccine that is 95% effective. Women and adults ≥65 were more accepting of a vaccine; Black Detroiters were less accepting. Believing vaccines to be important, effective, and safe was associated with higher acceptance. Uptake of a COVID-19 may be limited, depending on perceived vaccine effectiveness and general attitudes toward vaccines. Public health approaches to modifying these attitudes will be especially important in the Black community.