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Objectives: A systematic review was conducted to determine whether the etch-and-rinse or self-etching mode is the best protocol for dentin and enamel adhesion by universal adhesives. Data: This report followed the PRISMA Statement. A total of 10 articles were included in the meta-analysis. Sources: Two reviewers performed a literature search up to October 2014 in eight databases: PubMed, Web of Science, Scopus, BBO, SciELO, LILACS, IBECS and The Cochrane Library. Study selection: In vitro studies evaluating the bond strength of universal adhesives to dentin and/or enamel by the etch-and-rinse and self-etch strategies were eligible to be selected. Statistical analyses were conducted using RevMan 5.1 (The Cochrane Collaboration, Copenhagen, Denmark). A global comparison was performed with random-effects models at a significance level of p < 0.05. Results:The analysis of dentin micro-tensile bond strength showed no statistically significant difference between the etch-and-rinse and self-etch strategies for mild universal adhesives (p≥0.05). However, for the ultra-mild All-Bond Universal adhesive, the etch-and-rinse strategy was significantly different than the self-etch mode in terms of dentin micro-tensile bond strength, as well as in the global analysis of enamel micro-tensile and micro-shear bond strength (p≤0.05). Conclusions: The enamel bond strength of universal adhesives is improved with prior phosphoric acid etching. However, this effect was not evident for dentin with the use of mild universal adhesives with the etch-and-rinse strategy. Clinical significance: Selective enamel etching prior to the application of a mild universal adhesive is an advisable strategy for optimizing bonding. [ABSTRACT FROM AUTHOR]