Objectives: To systematically assess the literature and perform a meta-analysis wherever possible to answer the focused question “In patients with deep intrabony periodontal defects, what is the medium to long-term outcome (≥3y) of periodontal regenerative procedures comparing to open flap debridement in terms of clinical and/or radiographical outcome parameters?” Methods: Clinical trials (retro- & prospective case series with ≥5 patients, controlled-, and randomized controlled trials) reporting on clinical and/or radiographical parameters of periodontal regenerative procedures ≥3y post-operatively were systematically assessed for inclusion. Long-term clinical- (residual PPD; CAL gain; PPD reduction; REC increase) and radiographic- (bone gain; residual intrabony defect) parameters, and their changes between 1 year and long-term outcome, were extracted and/or calculated. Results: Seven retrospective studies, 14 case series, 3 CTs, and 27 RCTs were grouped into 2 observation periods, i.e. 3–5y and >5y after regenerative therapy, presenting data from 1394 and 618 sites, respectively. Analyses on Grafting, GTR, EMD, GTR+Grafting, EMD+Grafting, and EMD+GTR, and on OFD (from the control groups) showed that >5y after periodontal regenerative therapy in intrabony defects and irrespective the type of regenerative approach, CAL gain and PD reduction was about 1.5–2 times larger comparing to what was achieved with OFD (2.4-3.9mm vs. 1.5mm; 3.5-4.6mm vs. 2.7mm, respectively); residual PD after most of regenerative modalities was <5mm and about 1mm shallower than what was observed with OFD. Residual RDD after regenerative treatment was about ca. 2mm (i.e. 30–50%) shallower comparing to conventional surgery (1.4-2.9mm vs. 5.9mm, respectively). The clinical and radiographic improvements 1 year post-op, could be preserved on a long-term basis, with any changes being within 1mm. Conclusions: The additional clinical benefits of periodontal regenerative therapy over conventional periodontal surgery in intrabony defects remain largely stable on the long term. Grafting alone appears somehow less efficacious than GTR, EMD, GTR+grafting, or EMD+grafting on the long-term. Disclosure Statement: The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: none