The present study investigated the accuracy of intraoral scanners (IOSs) based on different image acquisition technologies in the field of presurgical orthopedic treatment (PSOT) in neonates with cleft palate.Dental casts of clinical situations representing unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), and cleft palate (CP) with reference polyetheretherketone (PEEK) scanbodies (Cares RC Mono Scanbody) were scanned utilizing four IOS systems: Carestream CS3600 (CS), Medit i500 (MD), Cerec Omnicam (CO), and Trios 3 (TS). One calibrated operator made five scans from each model using each IOS (N = 60). Reference digital impressions were obtained by an industrial-grade laboratory scanner (Sirona inEos X5) and superimposed using a best-fit algorithm. The divergence measure was extracted and the scanners were compared in terms of their accuracy using generalized least squares statistical models that account for variance heterogeneity. Additionally, comparative 3D analysis of the scans was performed using reverse engineering software (Geomagic Control X) in order to measure the discrepancy between the intraoral scans and the reference scan in five different anatomical regions of interest (ROIs): alveolar crest (AC), cleft (CL), palate (PL), vestibulum (VS), premaxilla (PM).The four IOSs showed relevant and significant differences in estimated trueness (P 0.001) and precision (P = 0.009). Among all anatomical models and analyzed ROIs, TS had the best accuracy (trueness: -1.57 µm; precision: 9.41 µm), followed by MD (trueness: -20.63 µm; precision: 29.18 µm), CS (trueness: -40.43 µm; precision: 16.52 µm) and CO (trueness: 81.27 µm; precision: 40.32 µm).Impression taking of the maxilla in cleft lip and palate patients is challenging for the operator. Relevant and significant differences in trueness and precision were found between the four IOSs. TS showed the best accuracy and was the least influenced under different anatomical ROIs. (Int J Comput Dent 2025;28(3):225-0; doi: 10.3290/j.ijcd.b5886430).