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Objective: A systematic review and meta-analysis was thus conducted to answer the following focused question based on PICO strategy: Is there any 3D matrix biomaterial used for root coverage of human Miller class I and II defects equivalent with the connective tissue graft in localized defects of at least 2 mm and 3 mm? Material and methods: The search on electronic database included MEDLINE, Cochrane Central Register of Controlled Trials, Clinical Trials.gov, Web of Science, and New Zealand/Australian Clinical Trials. Only randomized clinical trials (RCTs) that compared connective tissue graft (CTG) with at least one 3D matrix alone for root coverage in Class I and II Miller localized defects of at least 2 mm, with at least 6 months follow-up, were included in this systematic review. Results: A total of 14 studies were included for meta-analysis (12 compared CTG with acellular dermal matrix allograft and 2 compared CTG with Xenogenic Collagen Matrix). Relative root coverage showed no significant difference among the materials, for either 2 or 3 mm minimal recessions. For keratinized tissue width, on 2 mm recessions, CTG showed superiority above other biomaterials, but on 3 mm recessions, it seemed to have the same results. The percentage of recessions with complete root coverage for both 2 and 3 mm recessions showed similar results for all biomaterials. Conclusions: With their limits, the present data concluded that CTG, acellular dermal matrix allograft, and xenogenic collagen matrix provided similar results for root coverage. Clinical relevance: To know if there is a 3D matrix with equivalent predictable results for root coverage, that we could avoid the morbidity of the connective tissue graft for these cases. [ABSTRACT FROM AUTHOR]