Objectives We investigate determinants of SARS-CoV-2 anti-spike IgG responses in healthcare workers (HCWs) following one or two doses of Pfizer-BioNTech or Oxford-AstraZeneca vaccines . Methods HCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval . Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: [≥] 50 AU/ml). We used multivariable logistic regression to identify predictors of seropositivity and generalised additive models to track antibody responses over time . Results Vaccine uptake was 80%, but less in lower-paid roles and Black, south Asian and minority ethnic groups . 3570/3610 (98.9 %) HCWs were seropositive> 14 days post-first vaccination and prior to second vaccination , 2706/2720 (99.5 %) after Pfizer-BioNTech and 864/890 (97.1 %) following Oxford-AstraZeneca vaccines . Previously infected and younger HCWs were more likely to test seropositive post-first vaccination, with no evidence of differences by sex or ethnicity . All 470 HCWs tested> 14 days after second vaccine were seropositive . Quantitative antibody responses were higher after previous infection: median (IQR) > 21 days post-first Pfizer-BioNTech 14,604 (7644-22,291) AU/ml vs. 1028 (564-1985) AU/ml without prior infection (p <0.001). Oxford-AstraZeneca vaccine recipients had lower readings post-first dose compared to Pfizer-BioNTech, with and without previous infection , 10,095 (5354-17,096) and 435 (203-962) AU/ml respectively (both p <0.001 vs. Pfizer-BioNTech). Antibody responses post-second vaccination were similar to those after prior infection and one vaccine dose . Conclusions Vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs . Whether differences in response impact vaccine efficacy needs further study.