Background To evaluate the clinical outcomes 12 months after systemic administration of amoxicillin (AMX) and metronidazole (MET) adjunctive to subgingival debridement (SD) in patients with severe chronic periodontitis (sChP). Material and methods 102 patients with sChP were treated randomly as follows: SD within 2 consecutive days and placebo for 7 days (group A), SD+AMX+MET (both 500mg x3 times daily TID) for 3 days (group B), SD+AMX+MET (both 500mg x 3 TID) for 7 days (group C). At baseline, at 3-, 6-, and 12-months post-treatment probing pocket depth (PD), clinical attachment level (CAL), furcation involvement, bleeding on probing (BOP), full-mouth plaque score (FMPS) were determined. The reduction in the number of sites with PD >= 6mm was defined as main outcome variable. Results 75 patients completed the study. At 12 months, all three treatment groups showed statistically significant improvements (p<0.001) of mean PD, CAL, BOP and number of sites with PD >= 6mm compared to baseline. Mean residual PD were statistically significantly lower and CAL gain statistically significantly greater in the two antibiotic groups as compared to placebo. While PD reductions (p = 0.012) and CAL gain (p = 0.017) were statistically significantly higher in group C compared to group A, only the 3- day AB group showed statistically significantly fewer sites with PD >= 6mm at 12 m (p = 0.003). The reduction in the number of sites with PD >= 6 mm (primary outcome) showed no statistical significant differences between the 3 treatment groups. However, in both antibiotic groups significantly more patients compared to the placebo group reached a low risk for disease progression at 12 months (<= 4 sites with PD >= 5mm). Conclusion At 12 months, both adjunctive antibiotic protocols resulted in statistically significantly greater clinical improvements compared to placebo.