AIM: The aim of this study was to compare the clinical effects of Metronidazole (MTZ) combined with Amoxicillin (AMX) and repeated applications of antimicrobial photodynamic therapy (aPDT) as an adjuvant for the treatment of chronic periodontitis. METHODS: A double-blind controlled and randomized clinical trial was conducted in 34 patients. All of the patients were treated with scaling and root planing (SRP) and separated into 2 groups: the MTZ+AMX Group (n=17), who received SRP and the systemic use of MTZ (400mg 3xper day for 7days) and AMX (500mg 3xper day for 7days), and the aPDT Group (n=17), who received SRP and three aPDT applications at all sites with a probing depth>/=5mm immediately, at 48 and 96h after scaling and placebo pills over the span of 7days. Clinical examinations were performed at baseline and 90days post-therapy. The clinical parameters of bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) were measured. The aPDT was conducted using methylene blue and a low-level laser (GaAlAs 660nm, 100mW, 48s, and 160J/cm2) in all sites with a probing depth>/=5mm. A statistical analysis was also performed (alpha=5%). RESULTS: There was a significant improvement in CAL only in the intermediate pocket in the aPDT group compared to the MTZ+AMX group between baseline and 90days post-treatment (p=0.01). There was a reduction of both BOP and the percentage of residual pockets at 90days after treatment compared with baseline in both groups (p<0.05). CONCLUSION: Both proposed adjuvant therapies associated with conventional mechanical treatment in patients with chronic periodontitis were equally effective in terms of the gain of clinical insertion, control of inflammation and elimination of residual pockets.