This study evaluates the effectiveness of two Covid-19 vaccines, BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca), against the delta variant (B.1.617.2) and the alpha variant (B.1.1.7) in England. The study used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by these variants. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status. The effectiveness of one dose of vaccine was notably lower among persons with the delta variant (30.7%; 95% CI, 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7). With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. The study found that only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. The study was funded by Public Health England.This study evaluates the effectiveness of two Covid-19 vaccines, BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca), against the delta variant (B.1.617.2) and the alpha variant (B.1.1.7) in England. The study used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by these variants. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status. The effectiveness of one dose of vaccine was notably lower among persons with the delta variant (30.7%; 95% CI, 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7). With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. The study found that only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. The study was funded by Public Health England.