Outbreaks of invasive infections caused by group A β-hemolytic streptococcus (GAS) may occur in long-term care settings and are associated with a high case-fatality rate in debilitated adults. Targeted antibiotic treatment only to residents and staff known to be at specific risk of GAS may be an ineffective outbreak control measure. We describe two institutional outbreaks in which mass antibiotic treatment was used as a control measure. In the first instance, mass treatment was used after targeted antibiotic treatment was not successful. In the second instance, mass treatment was used to control a rapidly evolving outbreak with a high case-fatality rate. Although no further clinical cases were seen after the introduction of mass antibiotic treatment, persistence of the outbreak strain was documented in one institution >1 year after cases had ceased. Strain persistence was associated with the presence of a chronically colonized resident and poor infection control practices.