BACKGROUNDGrowing evidence suggests that COVID-19 vaccines differ in effectiveness against breakthrough infection or severe COVID-19, but vaccines have yet to be investigated in controlled studies that head-to-head compare immunity of one to another. This study compared protection offered by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer-BioNTech) vaccine in Qatar.METHODSIn a population of 1,531,736 vaccinated persons, two matched retrospective cohort studies were designed and used to investigate differences in mRNA-1273 and BNT162b2 vaccine protection, after the first and second doses, from December 21, 2020 to October 20, 2021.RESULTSAfter dose 1, cumulative incidence of breakthrough infection was 0.79% (95% CI: 0.75-0.83%) for mRNA-1273-vaccinated individuals and 0.86% (95% CI: 0.82-0.90%) for BNT162b2-vaccinated individuals, 21 days post-injection. Adjusted hazard ratio (AHR) for breakthrough infection was 0.89 (95% CI: 0.83-0.95; p=0.001). AHR was constant in the first two weeks at 1, but it declined to 0.67 (95% CI: 0.57-0.77; pCONCLUSIONSmRNA-1273 vaccination is associated with lower SARS-CoV-2 breakthrough infection and COVID-19 hospitalization and death than BNT162b2 vaccination, but the number of hospitalizations and deaths was exceedingly small for both vaccines. Both vaccines demonstrated strikingly similar patterns of build-up of protection after the first dose and waning of protection after the second dose.