Objectives: To investigate tooth-specific, clinical tooth-, and patient-related factors associated with tooth loss (TL) in patients with mild to severe periodontitis treated in a periodontal practice-based research network (Perio-PBRN) over at least 5 years. Materials and methods: The Perio-PBRN consists of five German periodontal practices where clinical data were collected regarding patient age, tooth type, bleeding on probing (BOP), pocket probing depth (PPD), furcation involvement (FI), number of attended appointments, and other variables of interest. The data were evaluated regarding factors influencing TL. Results: Data from 687 patients (aged 54.5 ± 11.1 years) with mild (N = 23, 3.35%), moderate (N = 247, 35.95%) or severe (N = 417, 60.70%) periodontitis and 15,931 teeth over a mean observation period of 6.83 ± 1.40 years per patient were gathered via the Perio-PBRN. In this period, a total of 657 teeth were lost (4.12%, overall TL: 0.14 ± 0.22 teeth/patient/y). The risk of TL was significantly increased for teeth with persistent PPD ≥ 6 mm (hazard ratio: 6.81 [95% confidence interval: 5.07–9.15] in comparison to PPD < 4 mm. Additionally, BOP (3.90 [2.46–6.19]), furcation involvement, jaw, age and tooth type showed a significant influence on TL, while number of visits were not significantly associated with TL. Conclusions: Periodontal care of patients with moderate to severe disease in specialized practices was associated with a low rate of TL. Known tooth-related prognostic factors were confirmed. However, the results must be interpreted cautiously without knowledge of risk factors such as smoking and diabetes. Clinical relevance: PBRNs can help gather large amounts of periodontal practice-level data. Trial registration: The study was registered in the German Clinical Trials Register (DRKS 00011448).