Periapical surgery focuses on the treatment of teeth with persistent periapical lesions when orthograde root canal treatment fails. Although MTA® is the gold standard material for retrograde filling, Biodentine® - a tricalcium silicate-based cement - has been proposed in order to resolve several of its limitations. A systematic review has been carried out to compare the physicochemical properties of Biodentine® versus MTA® as root-end filling material in periapical surgery. An electronic search was conducted by two independent examiners during March 2020 in the Cochrane, PubMed-MEDLINE and Scopus databases. In addition, a manual search was made in specialized journals. Comparative human or in vitro studies that evaluated bond strength, the presence of marginal gap and sealing ability were included. No restriction on publication date was applied. Animal studies, clinical cases, cases series and expert opinions were excluded. After analyzing 147 initially selected studies, 13 publications were included. Regarding bond strength, the studies seemed to evidence better performance of Biodentine® in both acidic and blood contaminated environments. In relation to the presence of marginal gap and sealing ability, the studies yielded contradictory results. According to some authors, the sealing ability of Biodentine® is greater than that of MTA® during the first 24 hours, though both materials prove equal after one week. Other authors recorded no significant differences. Considering the limitations and heterogeneity of the studies included, there is not sufficient evidence to confirm the clinical superiority of Biodentine® as a root-end filling material in periapical surgery.