Objective: Prevention of tooth loss and maintaining favorable periodontal status are the ultimate goals of periodontal therapy. The aim of this study was to evaluate the effectiveness of non-surgical periodontal therapy and supportive periodontal care in arresting the progression of chronic periodontitis and in preventing tooth loss. Materials and methods: Periodontal charts, self-reported medical history, and two interleukin-1 (IL-1) polymorphism genotypes of 100 patients were obtained from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository after screening 4,825 subjects. We used tooth loss (TL) and clinical attachment loss (CAL) as outcomes of disease affection in our analysis. In our study, we have included third molars, teeth lost during active periodontal treatment (APT), and those lost during the supportive periodontal program. All subjects had at least 12 months of follow-up. Fisher’s exact test was used to investigate the association between tooth loss and different risk factors. Paired t-test was conducted to detect the difference in means of CAL at baseline and at final assessment. Results: There were 59 patients (36 males and 23 females with an average age of 52 years) that lost at least one tooth during supportive periodontal care. Tooth mortality rate declined by more than half in patients who enrolled in a supportive periodontal program for six years compared to those who dropped out after one year (0.52 vs. 3.4 teeth/patient/year, respectively). Increased risk of tooth loss was found to be associated with diabetes (p=0.01), as well as high blood pressure (p<0.0001). We did not find an association between tooth loss and polymorphisms in interleukin IL-1α/IL-1β (rs1800587, p=0.36 and rs1143634, p=0.51, respectively). During the first and the second year of supportive periodontal treatment, the clinical attachment loss decreased by 0.36 mm and 0.34 mm, respectively (p=0.025 and p=0.0697), when compared to baseline measurements. Moreover, a slight increase in CAL was found in the group of patients who attended regular periodontal maintenance program for six years (p=0.037, difference of 0.38 mm in comparison to the baseline measurement). Conclusion: Our findings suggested that supportive periodontal therapy is effective for the long-term preservation of teeth and the stability of periodontal tissue in patients with advanced chronic periodontitis.