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BACKGROUND The aim of this prospective study is to evaluate the clinical applicability of the entire papilla preservation technique (EPP) in the regenerative treatment of isolated deep intrabony defects using native collagen membrane and bone grafting materials. METHODS Fifteen healthy and non-smoker patients (nine males and six females; mean age: 47.73±12.18; range 21-63 years) with one isolated deep intrabony defect each (baseline probing depth (PD): 9.03±1.62 mm; clinical attachment level (CAL): 11.16±1.81 mm) were treated with guided tissue regeneration. Surgical access to the defect was provided by a single buccal vertical incision with an interdental tunnelling flap. Following the granulation tissue removal, intrabony defect was filled with bone substitutes. A collagen barrier was trimmed and placed under the intact defect-associated papilla with palatal positioning suture. Microsurgical sutures were used for primary closure. RESULTS At 1 week, healing of the 15 sites was uneventful. During the study, all sites showed 100% primary closure rate. At 1-year follow-up, an average CAL gain of 5.86±1.28 mm (p<0.0001), PD reduction of 6.1±1.47 mm (p<0.0001), and minimal increase in gingival recession of 0.23±0.62 mm (p = 0.168) were observed. CONCLUSION This novel surgical technique, that keeps the interdental papilla intact, seems promising to provide optimal biomaterial protection and healing conditions, even when a collagen barrier and bone substitutes are applied. This article is protected by copyright. All rights reserved.