Aims: Complete maxillary edentulism and prosthetic rehabilitation with removable full dentures are known to affect speech intelligibility. The aim of this study was to prospectively investigate the long-term effect of time on speech intelligibility in patients being rehabilitated with newly fabricated full maxillary dentures. Materials and Methods: Speech was recorded in a group of 14 patients (male = 9, female = 5; mean age ± standard deviation [SD] = 66.14 ± 7.03 years) five times within a mean period of 4 years (mean ± SD: 47.50 ± 18.16 months; minimum/maximum: 24/68 months) and in a control group of 40 persons with healthy dentition (male = 30, female = 10; mean age ± SD = 59 ± 12 years). All 14 participants had their inadequate removable full maxillary dentures replaced with newly fabricated dentures. Speech intelligibility was measured by means of a polyphone-based speech recognition system that automatically computed the percentage of accurately spoken words (word accuracy [WA]) at five different points in time: 1 week prior to prosthetic maxillary rehabilitation (both with and without inadequate dentures in situ) and at 1 week, 6 months, and a mean of 48 months after the insertion of newly fabricated full maxillary dentures. Results: Speech intelligibility of the patients significantly improved after 6 months of adaptation to the new removable full maxillary dentures (WA = 66.93% ± 9.21%) compared to inadequate dentures in situ (WA = 60.12% ± 10.48%). After this period, no further significant change in speech intelligibility was observed. After 1 week of adaptation, speech intelligibility of the rehabilitated patients aligned with that of the control group (WA = 69.79% ± 10.60%) and remained at this level during the examination period of 48 months. Conclusion: The provision of new removable full maxillary dentures can improve speech intelligibility to the level of a healthy control group on a long-term basis.