ObjectivesThe aim of the present systematic review and meta-analysis is to assess the accuracy of automated landmarking using deep learning in comparison with manual tracing for cephalometric analysis of 3D medical images.MethodsPubMed/Medline, IEEE Xplore, Scopus and ArXiv electronic databases were searched. Selection criteria were: ex vivo and in vivo volumetric data images suitable for 3D landmarking (Problem), a minimum of five automated landmarking performed by deep learning method (Intervention), manual landmarking (Comparison), and mean accuracy, in mm, between manual and automated landmarking (Outcome). QUADAS-2 was adapted for quality analysis. Meta-analysis was performed on studies that reported as outcome mean values and standard deviation of the difference (error) between manual and automated landmarking. Linear regression plots were used to analyze correlations between mean accuracy and year of publication.ResultsThe initial electronic screening yielded 252 papers published between 2020 and 2022. A total of 15 studies were included for the qualitative synthesis, whereas 11 studies were used for the meta-analysis. Overall random effect model revealed a mean value of 2.44 mm, with a high heterogeneity (I2= 98.13%,τ2= 1.018,p-value < 0.001); risk of bias was high due to the presence of issues for several domains per study. Meta-regression indicated a significant relation between mean error and year of publication (pvalue = 0.012).ConclusionDeep learning algorithms showed an excellent accuracy for automated 3D cephalometric landmarking. In the last two years promising algorithms have been developed and improvements in landmarks annotation accuracy have been done.