In December 2020, the University of California San Diego Health (UCSDH) workforce experienced a dramatic increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Vaccination with mRNA vaccines began in mid-December 2020; by March, 76% of the workforce had been fully vaccinated, and by July, the percentage had risen to 87%. Infections had decreased dramatically by early February 2021. Between March and June, fewer than 30 health care workers tested positive each month. However, coincident with the end of California’s mask mandate on June 15 and the rapid dominance of the B.1.617.2 (delta) variant that first emerged in mid-April and accounted for over 95% of UCSDH isolates by the end of July (Figure 1), infections increased rapidly, including cases among fully vaccinated persons. Institutional review board approval was obtained for use of administrative data on vaccinations and case-investigation data to examine mRNA SARS CoV-2 vaccine effectiveness.