Abstract Background We aimed to estimate vaccine effectiveness against infection (VE-infection) and against further transmission (VE-infectiousness) in a household setting during Delta and Omicron. Knowing these effects can aid policy makers in deciding which groups to prioritize for vaccination. Methods Participants with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test were asked about coronavirus disease 2019 (COVID-19) vaccination status and SARS-CoV-2 testing of their household members 1 month later. VE-infection and VE-infectiousness were estimated using generalized estimating equation logistic regression adjusting for age, vaccination status, calendar week, and household size. Results A total of 3399 questionnaires concerning 4105 household members were included. During the Delta period, VE-infection and VE-infectiousness of primary series were 47% (95% confidence interval [CI], −27% to 78%) and 70% (95% CI, 28% to 87%), respectively. During the Omicron period, VE-infection was −36% (95% CI, −88% to 1%) for primary series and −28% (95% CI, −77% to 7%) for booster vaccination. VE-infectiousness was 45% (95% CI, −14% to 74%) for primary series and 64% (95% CI, 31% to 82%) for booster vaccination. Conclusions Our study shows that COVID-19 vaccination is effective against infection with SARS-CoV-2 Delta and against infectiousness of SARS-CoV-2 Delta and Omicron. Estimation of VE against infection with SARS-CoV-2 Omicron was limited by several factors. Our results support booster vaccination for those in close contact with vulnerable people to prevent transmission.