The Covid-19 disease is resurging across the United States and vaccine hesitancy remains a major obstacle to reaching the expected threshold for herd immunity. Using the nationally representative cross sectional Household Pulse Survey (HPS) Data published by the U.S. Census Bureau, this study identified demographic, socio-economic, and medical-psychological determinants of Covid-19 vaccination. Results revealed significant differences in Covid-19 vaccine uptake due to age, sex, sexual orientation, race or ethnicity, marital status, education, income, employment form, housing and living condition, physical illness, mental illness, Covid-19 illness, distrust of vaccines and beliefs about the efficacy of vaccines. Government policymakers need to be cognizant of these determinants of vaccine hesitancy when formulating policies to increase vaccine uptake and control the COVID-19 pandemic. The findings of this study suggest that segmented solutions to reach vulnerable groups like racial minorities and homeless people are needed to win the trust and optimize vaccine uptake.