The aim of this investigation was to evaluate the effectiveness of collagen cross-linking agents (CCLAs) used in combination with the adhesive technique in restorative procedures.

In this systematic review, the authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. An electronic search was performed using PubMed, Scopus, Web of Science, Cochrane Library, LILACS, and DOSS, up to October 2020. The gray literature was also researched. Only randomized clinical trials were selected.

The selection process yielded 3 studies from the 838 retrieved. The addition of CCLAs in the retention of restorations increased the number of events. The postoperative sensitivity scores and marginal adaptation scores showed no significant difference between the CCLA and control groups, and the marginal pigmentation scores showed a significant increase in the CCLA group. There were no caries events in any group throughout the evaluation period.

This systematic review showed that there is no clinical efficacy to justify the use of CCLAs in the protocols performed.