The present systematic review analyzed the current literature to investigate whether rapid maxillary expansion (RME) causes radicular resorption, assessed by cone-beam computed tomography (CBCT). Eighteen electronic databases and reference lists of studies were searched up to November 2017. Grey literature was also screened. To be included, articles must be human studies on growing subjects with transversal maxillary deficiency treated with maxillary expansion protocol and with 3-D radiographic assessment of radicular volume by CBCT images. Two authors independently performed study selection, data extraction, and risk of bias assessment. Study characteristics (study design, sample size, age, sex, skeletal maturity, type of appliance, daily activation, teeth evaluated, CBCT settings), and study outcomes (radicular volume loss) were reported according to the PRISMA statement. Only 3 articles were considered eligible and an individual analysis of the selected articles was undertaken. The risk of bias assessment revealed low methodological quality for all the studies included. In all the considered studies, significant radicular volume loss was observed in posterior teeth, following RME. When reported in percentage, the radicular volumetric loss was similar between anchored (first molars and first premolars) and unanchored teeth (second premolars). A preliminary evaluation of the patient-related risk factors for RR is warmly advisable when administering RME.