Composite resin is used extensively for restoration of teeth with vital pulps. Although cell culture studies have disclosed harmful effects on pulpal cells, any untoward clinical effects, manifest as adverse pulpal responses, have yet to be determined. This study comprises a systematic review, designed to address the question of whether the risk of endodontic complications is greater with composite resin restorations than with other restorative materials, such as amalgam. The study methodology involved (i) formulation of the research question, (ii) construction and conduct of an extensive literature search with (iii) interpretation and assessment of the retrieved literature. A search of the medical database PubMed was complemented with a search of the Controlled Trials Register (CENTRAL). The initial search yielded 1043 publications, the abstracts of which were read independently by the authors. After additional searches, 10 studies were included in the review. In all the included studies, the level of evidence was assessed as low. No conclusions could therefore be drawn. The included studies reported few, if any, endodontic complications. Little or no differences emerged between teeth restored with composite resins and those restored with amalgam. To determine whether composite resin restorations of teeth with vital pulps are associated with an increased risk for development of endodontic complications such as apical periodontitis, further evidence is needed, from well-constructed studies with a large number of participants.