To investigate the effects of the manufacturing technologies on the surface (cameo and intaglio) accuracy (trueness and precision) of computer-aided design and computer-aided manufacturing (CAD-CAM) occlusal splints. The digital design of the master occlusal splint was designed in a CAD software program. Six groups (n = 10) were tested in this study, including Group 1- Milling (Wax), Group 2- Heat-polymerizing, Group 3- Milling (M series), Group 4- Milling (DWX-51/52D), Group 5- 3D-printing (Cares P30), and Group 6- 3D-printing (M2). The study samples were placed in a scanning jig fabricated from putty silicone and Type III dental stone. The study samples were then scanned with a laboratory scanner at the intaglio and cameo surfaces, and the scanned files were exported in standard tessellation language (STL) file format. The master occlusal splint STL file, was used as a reference to compare with all scanned samples at the intaglio and cameo surfaces in a surface matching software program. Root mean square (RMS, measured in mm, absolute value) values were calculated by the software for accuracy comparisons. Group means were used as the representation of trueness, and the standard deviation for each group was calculated as a measure of precision. Color maps were recorded to visualize the areas of deviation between study samples and the master occlusal splint file. The data were normalized and transformed to rank scores, and one-way ANOVA was used to test for the differences between the groups. Pairwise comparisons were made between different groups. Fishers least square differences were used to account for the family-wise error rate. A 5% significance level was used for all the tests. The null hypotheses were rejected. The manufacturing technologies significantly affected the trueness of occlusal splints at both intaglio and cameo surfaces (p< 0.001). At the cameo surfaces, Group 1- Milling (Wax) (0.03 ± 0.02mm), Group 3- Milling (M series) (0.04 ± 0.01mm), and Group 4- Milling (DWX-51/52D) (0.04 ± 0.01mm) had the smallest mean RMS values and highest trueness. Group 3 had the smallest standard deviation and highest precision among all groups (p< 0.001, except p = 0.005 when compared with Group 2). Group 5 had the largest standard deviation and lowest precision among all groups (p< 0.001). At the intaglio surfaces, Group 1- Milling (Wax) (0.06 ± 0.01mm) had the smallest RMS values and highest trueness among all groups (p< 0.001), and Group 2- Heat-polymerizing (0.20 ± 0.03mm) and Group 5- 3D-printing (Cares P30) (0.15 ± 0.05mm) had significantly larger mean RMS and standard deviation values than all other groups (p< 0.001), with lowest trueness and precision. In the color maps, Group 2- Heat-polymerizing and Group 5- 3D-printing (Cares P30) showed the most discrepancies with yellow and red (positive discrepancies) in most areas, and Group 1- Milling (Wax) showed the best and most uniform surface matching with the most area in green. The manufacturing technologies significantly affected the trueness and precision of occlusal splints at both intaglio and cameo surfaces. The 5-axis milling units and industrial-level CLIP 3D-printer could be considered to achieve surface accuracy of occlusal splints.