BACKGROUND: Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge. METHODS: We analyzed data from 3 cohort studies spanning 1 September 2022 to 31 July 2023 to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs irrespective of symptoms, participated in annual blood draws, and completed periodic surveys, which included vaccination status and infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated by Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination. RESULTS: Among 3344 adults, the adjusted VE of a bivalent vaccine against infection was 37.2% (95% CI, 12.3%-55.7%) within 7 to 59 days of vaccination and 21.1% (95% CI, -0.5% to 37.1%) within 60 to 179 days of vaccination when compared with participants who were unvaccinated or had received an original monovalent vaccine dose ≥180 days prior. Overall, the adjusted VE of a bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI, 46.0%-74.5%) within 7 to 179 days of vaccination and 39.4% (95% CI, 12.5%-61.6%) at ≥180 days when compared with naive participants who were unvaccinated or had received a monovalent vaccine dose ≥180 days prior. CONCLUSIONS: Adults with prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.