AIM To assess the effect of systemic azithromycin as a supplement to scaling and root planing (SRP) in the treatment of aggressive periodontitis (AgP). MATERIAL AND METHODS Twenty-four individuals (13-26 years old) underwent a plaque control program, and then were treated with SRP. Subjects were assigned randomly into two groups; the test group used 500 mg azithromycin once a day for 3 days, whereas the control group used a placebo. Clinical variables were assessed at baseline, 3, 6, 9, and 12 months. The periodontal status at baseline and 12 months was compared using the Wald test, and adjusting for the effect of clustering of teeth within subjects. RESULTS There were no significant differences in visible plaque, gingival bleeding, and supragingival calculus between groups throughout the study. Periodontal probing depth (PPD) and clinical attachment level improved significantly from baseline to 12 months in both groups, with the test group showing significantly more reduction in mean PPD compared with controls (2.88 mm versus 1.85 mm, respectively, p=0.025). Subjects administering azithromycin showed a higher percentage of teeth with attachment gain >or=1 mm (81.34 versus 63.63, p=0.037), whereas the controls had higher percentage of teeth with attachment loss >or=1 mm (11.57 versus 2.24, p=0.015). CONCLUSIONS The adjunctive use of azithromycin has the potential to improve periodontal health of young patients with AgP.