A nationwide laboratory-based surveillance study of invasive Streptococcus pyogenes infections was conducted in Germany. Invasive isolates (n=586) were obtained between 2003 and 2007. Most isolates were obtained from blood (53.9%) or skin lesions (17.6%). The most common emm types were emm 1 (30.5%), emm 28 (18.3%) and emm 3 (9.6%). Overall, speA was positive in 45.9%, speC in 44.7% and ssa in 14.8% of isolates. SpeA was common in emm type 1 (100%) and emm type 3 (96.4%), whereas speC was often observed in emm type 28 (93.5%). The most frequent clinical manifestations included sepsis (40.1%), necrotizing fasciitis (20.8%) and streptococcal toxic shock syndrome (16.6%). All isolates were susceptible to penicillin G, cefotaxime and levofloxacin. Tetracycline shows the highest rate of resistant or intermediate isolates with 11.6%, followed by clarithromycin (5.5%) and clindamycin (1.2%). The most prominent trend is the reduction of tetracycline-nonsusceptible isolates from 18.6% in 2003 to 8.9% in 2007.