Purpose: To assess the retention and adaptation of milled and printed denture bases in comparison to conventional ones. Materials and Methods: A total of 24 completely edentulous patients were selected. For each patient, three maxillary denture bases were constructed according to different fabrication techniques, thus defining the three groups for comparison: group 1 consisted of denture bases constructed by a conventional technique, group 2 consisted of denture bases milled from prepolymerized blocks of PMMA, and group 3 consisted of denture bases fabricated by a 3D printing technique. A digital force gauge was used for measuring the retention of the denture bases intraorally, while Geomagic Control X 64 software was used to evaluate the adaptation of the denture bases with their corresponding master casts. Repeated-measures analysis of variance was used for comparison among the groups, followed by pairwise comparison with post hoc Bonferroni correction. The significance level was set at α = .05. Results: Statistical analysis showed significant differences among the three groups regarding retention and adaptation. The highest values of retention and adaptation of denture bases were found in group 2 (milling group). Conclusion: Within the limitations of this study, the following could be concuded: milled denture bases demonstrated better retention and adaptation than the conventional heat-polymerized and printed denture bases, and the printed denture bases showed better adaptation but similar retention to conventional heat-polymerized denture bases.