Univariate approaches have identified single factors influencing periodontal disease progression. The aim of this explorative approach was to assess the influence of various predictive factors responsible for the prevention of periodontal disease progression in the same patient sample. Patients with untreated chronic periodontitis underwent subgingival debridement alone or in combination with adjunctive antimicrobial therapy (systemic amoxicillin and metronidazole/7 days plus supragingival CHX irrigation). Supportive periodontal therapy was performed over a 24-month period. As predictors, clinical, microbial, immunological, and genetic parameters were assessed. The primary outcome variable was the percentage of teeth without attachment loss >/=2 mm over the study period (stability of attachment). At 24 months, multiple regression analysis identified adjunctive antimicrobial therapy for teeth with initially at least one site showing a pocket probing depth of >/=7 mm and IgG(4) reactivity against a 110-kDa protein of A. actinomycetemcomitans at teeth with initial pocket probing depths </=6 mm as main predictors of long-term attachment stability ( p<0.05). Other parameters failed to influence treatment outcome. Adjunctive antimicrobial therapy and antibody reactivity may be dominant factors influencing the prevention of attachment loss in patients receiving periodontal therapy.