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Purpose: To evaluate through a systematic review and meta-analysis whether the immediate and long-term bonding performance of universal adhesives would be improved by prior acid etching. Materials and Methods: Two reviewers performed a literature search up to April 2018 in eight databases: PubMed, Web of Science, Cochrane Library, SciELO, Scopus, LILACS, IBECS, and BBO. Only studies that evaluated the dentin or enamel bond strength of universal adhesives using a self-etch or etch-and-rinse strategy were included. Analyses were carried out using RevMan 5.3.5 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). A global analysis comparing self-etch or etch-and-rinse strategies and the influence of aging on bonding performance was performed with random-effects models at a significance level of p < 0.05. Results: A total of 59 in vitro studies were included in the meta-analysis. The enamel bond strength of universal adhesives was improved by the etch-and-rinse approach (p < 0.05). In dentin, this effect was observed for ultramild and intermediately strong universal adhesives (p < 0.05). Irrespective of the strategy employed, intermediately strong adhesives showed a decrease in bond strength after all types of aging. This effect was also observed for ultra- mild universal adhesives used in the etch-and-rinse approach (p < 0.05). Mild universal adhesives showed bond strength stability in both strategies (p > 0.05). Conclusions: The in vitro evidence suggests that bonding performance of mild universal adhesives can be improved by using the selective enamel-etch strategy. Mild universal adhesives seem to be the more stable materials, in both etch-and-rinse or self-etch strategies. [ABSTRACT FROM AUTHOR]