Scaling and root planing in conjunction with systemic administration of antibiotics is used for treatment of aggressive periodontitis. The study investigated the changes of the subgingival microbiota in a homogeneous cohort of 12 female Caucasian patients. Plaque samples were obtained from 4 defined deep lesions per patient at baseline and 2, 6, and 12 months after therapy (mechanical plaque removal, oral administration of amoxicillin and metronidazole). Amplification of the 16S rRNA gene, cloning, and sequencing were applied to identify microbial species. Porphyromonas gingivalis strains were typed by multilocus sequence typing. Despite of a favorable clinical outcome, 16S rRNA sequence analysis revealed only minor changes of the microbiota with a temporal reduction of P. gingivalis and of Treponema denticola-like phylotypes. In contrast to T. denticola, T. sokranskii-like phylotypes were not affected. In 4 patients with recurrent colonization by P. gingivalis, the bacterial clones were identical before and after therapy as evidenced by multilocus sequence typing suggesting clonal persistence or reinfection during the course of the study. In summary, despite a favorable clinical outcome, a transient effect on only few bacterial species was observed.