Objective: The aim of this study was to evaluate adjunctive effect of hormone replacement therapy (HRT) on non-surgical periodontal therapy in postmenopausal women with moderate to severe chronic periodontitis. Method: A total of 28 postmenopausal female were recruited for this parallel, single-blinded study. 13 were under HRT (test group, mean age = 50.8 years) and 15 were never exposed to any HRT (control group, mean age = 54.1 years). The mean duration of menopause was 3.6 years for test subjects and 3.0 years in controls. Clinical parameters, including presence of supragingival plaque (Pl%), bleeding on probing (BOP%), probing pocket depth (PPD) and probing attachment level (PAL) were recorded at baseline and 3 months after non-surgical periodontal treatment. Results: Full mouth Pl% decreased from 76% at baseline to 25% at 3-month in the test group and from 75% to 29% in the control group while the BOP% decreased from 69% to 31% in test and 74% to 28% in control groups, respectively. Mean PPD reductions for test and control groups were 0.75mm and 0.95mm, mean PAL gains were 0.34mm and 0.41mm and mean increases in recession were 0.40mm and 0.53mm, respectively. No statistically significant differences in PPD reduction, PAL gain and increase in recession were found between test and control groups using independent t-test (p>0.05). Conclusion: The present study did not show any adjunctive clinical effect of HRT on 3-month periodontal treatment responses in postmenopausal women with moderate to severe chronic periodontitis.