Abstract Aim The aim of this study was to assess the effect of systemic antibiotic therapy on the treatment of aggressive periodontitis (AgP). Methods This study was conducted and reported in accordance with the PRISMA statement. The MEDLINE , EMBASE and CENTRAL databases were searched up to June 2014 for randomized clinical trials comparing the treatment of subjects with AgP with either scaling and root planing ( SRP ) alone or associated with systemic antibiotics. Bayesian network meta‐analysis was prepared using the Bayesian random‐effects hierarchical models and the outcomes reported at 6‐month post‐treatment. Results Out of 350 papers identified, 14 studies were eligible. Greater gain in clinical attachment ( CA ) (mean difference [ MD ]: 1.08 mm; p < 0.0001) and reduction in probing depth ( PD ) ( MD : 1.05 mm; p < 0.00001) were observed for SRP + metronidazole (Mtz), and for SRP + Mtz + amoxicillin (Amx) ( MD : 0.45 mm, MD : 0.53 mm, respectively; p < 0.00001) than SRP alone/placebo. Bayesian network meta‐analysis showed additional benefits in CA gain and PD reduction when SRP was associated with systemic antibiotics. Conclusions SRP plus systemic antibiotics led to an additional clinical effect compared with SRP alone in the treatment of AgP. Of the antibiotic protocols available for inclusion into the Bayesian network meta‐analysis, Mtz and Mtz/Amx provided to the most beneficial outcomes.