Vaccination and non-pharmaceutical interventions during COVID-19: Impact on health and non-health outcomes in the US

•We examined the relative effectiveness of vaccination and NPIs on health outcomes and unemployment rate in the US.•The interaction between vaccinations and NPIs had a negative association with COVID-19 cases and deaths, implying some restrictions might be required even during vaccination campaigns and new variant surges.•Vaccinations had a negative association with the unemployment rate in the US, but the Omicron variant surge had a positive association with the total unemployment rate.•Policymakers should determine the optimal mix of NPIs and vaccinations to balance health and economic impacts, considering the potential psychological problems at the individual level.