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Purpose: To evaluate the in vitro bond strength of universal adhesive systems to indirect substrates. Material and Methods: Two reviewers performed a literature search up to March 2018 in seven databases: PubMed, Web of Science, SciELO, Scopus, LILACS, IBECS, and BBO. The review included studies that compared the bond strength of universal adhesives and well-established material-specific primers to indirect substrates: lithium disilicate ceramic, yttrium-stabilized zirconium dioxide ceramic, leucite-reinforced ceramic, feldspathic porcelain, polymer infiltrated ceramic material, resin composite or metal alloys. Analyses were carried out using RevMan 5.3.5. A global comparison was performed with the standardized mean difference using a random-effects models at a significance level of p < 0.05. Results: A total of 45 studies were included in the qualitative analysis, and the meta-analysis was performed with 42 studies. Bond strength to glass-based ceramics and alloys was improved with the use of a specific-primer as separate step before the bonding procedures (lithium disilicate, p < 0.001; alloys, p < 0.001). The bond strength to zirconium substrates was improved with the use of universal adhesives (p < 0.001). For bond strength to composite resin as indirect substrate, universal adhesives performed in a manner similar to that of the material-specific primer (p = 0.11). Conclusions:The clinical procedure of luting zirconia and resin composite restorations could be simplified by using single-bottle universal adhesives. However, the ability of universal adhesives to achieve an adequate and durable bond to glass-based ceramics and alloys appears to be limited.