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Purpose: The aim of this long-term cohort study was to evaluate the efficacy and complications of fixed partial dentures in a convenience sample of 100 patients with periodontal disease who were treated and maintained periodontal patients after 20 years. Materials and Methods: After active treatment, including periodontal surgery and endodontic and prosthetic treatment, patients were enrolled in a supportive periodontal care (SPC) program with 3- to 6-month recalls. All patients showed clinical data recorded at (1) the original consultation (T0), (2) the first SPC visit following the completion of prosthetic treatment (T1), and (3) at the latest SPC clinical session 20 years after T1 (T2). Multivariate analyses were performed to investigate the influence of clinical variables on the risk of prosthetic abutment (PA) loss after 20 years' visits. Results: The final sample comprised 100 patients. At T1, a total of 948 PAs represented the original sample of experimental teeth. At the 20-year follow-up, a total of 854 PAs (90.1%) were still in function, while 94 (9.9%) PAs in 41 patients (41%) were lost during SPC; 98% of lost PA were endodontically treated. Vertical root fracture (48%) was the major cause of PA loss, while progression of periodontitis caused 31% of PA loss. Age (P = .002), Full-Mouth Plaque Score (P .0001), Full-Mouth Bleeding Score (P = .0002), and oral parafunctions (P = .0083) were associated with increased probability of PA failure. Among clinical-related factors, endodontic treatment (P = .0082), root resection/ amputation (P .0001), multi-rooted teeth (P = .0005), and abutment associated with parafunction (P .0001) were associated with increased risk of abutment loss after 20 years. Conclusions: Perioprosthetic treatment in compliant patients is highly successful after 20 years of SPC.