Purpose: To evaluate the effect of immersion in water on deformation of maxillary denture bases created with CAD/CAM and heat-polymerized resin fabrication techniques under loading condi8ons. Materials and Methods: 2-mm-thick denture bases were fabricated using four techniques: CAD/CAM milling (CCM; Polywax PMMA blank, Yamachi PMMA disk Yamahachi Dental); 3D prin8ng (3DP; BV005, NextDent Base); compression molding (CM; Luciton 199, Dentsply Sirona); and injec8on molding (IM; Ivobase, Ivoclar; n = 5 per group). Three static 49-N loads were applied perpendicular to each denture base, and the mean strain  value (MSV) was recorded with strain gauges a[ached to the denture surface. The denture bases were stored at 37°C in distilled water for 14 and 28 days, and the MSVs under the same static load were recorded. Results: The highest MSVs were observed at the posterior palatal seal, tuberosity, and labial notches of the dentures. The lowest MSVs were recorded for the CCM group and then the CM and IM groups. The highest MSVs were recorded for the 3DP group. No significant differences in regional MSVs (P > .05) were observed among the CCM, CM, and IM aber 14 and 28 days in water. Large devia8ons in MSVs were recorded for the 3DP group across the measurement sites aber water exposure (P < .05). Conclusions: CCM had the lowest denture deformation under static loading. After immersion in water, the deformation changes under static loading were stable for CCM, CM, and IM. However, variations among the materials used in 3DP group influenced the mechanical performance and presented larger deformations.