Severe invasive group A streptococcal (GAS) disease is believed to have reemerged during the past 10-20 years. We conducted active, laboratory, population-based surveillance in 5 US states (total population, 13,214,992). From 1 July 1995 through 31 December 1999, we identified 2002 episodes of invasive GAS (3.5 cases per 100,000 persons). Rates varied by age (higher among those <2 or >/=65 years old), surveillance area, and race (higher among black individuals) but did not increase during the study period. The 5 most common emm types (1, 28, 12, 3, and 11) accounted for 49.2% of isolates; newly characterized emm types accounted for 8.9% of isolates. Older age; presence of streptococcal toxic shock syndrome, meningitis, or pneumonia; and infection with emm1 or emm3 were all independent predictors of death. We estimate that 9600-9700 cases of invasive GAS disease occur in the United States each year, resulting in 1100-1300 deaths.