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Objective: The objective of this review is to evaluate the clinical outcomes of standard periradicular surgery versus periradicular surgery with the use of guided tissue regeneration techniques involving blood-derived products in patients undergoing periradicular surgery. Introduction: Guided tissue regeneration techniques have been available in dentistry for decades. Primarily used during periodontal surgery and implant placement, their usefulness in periapical surgery has been garnering increased attention. According to current available evidence, guided tissue regeneration can improve clinical patient outcomes. No systematic reviews have been carried out to investigate guided tissue regeneration techniques involving blood-derived products in periradicular surgery. Inclusion criteria: Randomized controlled trials that investigate the outcomes of guided tissue regeneration techniques involving blood-derived products versus standard periradicular surgery technique, will be included for review. Studies will be excluded if they contain patients who have previously undergone periradicular surgery or the treatment was carried out on unrestorable teeth (ie, due to periodontal disease or root fractures). Methods: The databases MEDLINE, Embase, Dentistry and Oral Sciences Source, and Cochrane CENTRAL will be used to locate published reports of studies. Reference lists of relevant past systematic reviews will be used to identify further studies. Unpublished studies will be sought using international trials registries and repositories. Two reviewers will carry out independent screening of records for inclusion and the selected studies will be critically appraised prior to data extraction and synthesis. Meta-analysis will be performed if appropriate. Systematic review registration number: PROSPERO CRD42020222663