Antibiotics are often used in the treatment of chronic periodontitis, which is a major cause of tooth loss. However, evidence in favour of a microbial indication for the prescription of antibiotics is lacking, which may increase the risk of the possible indiscriminate use of antibiotics, and consequent, microbial resistance. Here, using an open-ended technique, we report the changes in the subgingival microbiome up to one year post-treatment of patients treated with basic periodontal therapy with or without antibiotics. Antibiotics resulted in a greater influence on the microbiome 3 months after therapy, but this difference disappeared at 6 months. Greater microbial diversity, specific taxa and certain microbial co-occurrences at baseline and not the use of antibiotics predicted better clinical treatment outcomes. Our results demonstrate the predictive value of specific subgingival bacterial profiles for the decision to prescribe antibiotics in the treatment of periodontitis, but they also indicate the need for alternative therapies based on ecological approaches.