Aim: The purpose of this study was to evaluate and compare neutral-zone CAD/CAM dentures and conventionally fabricated heat-polymerized dentures; by assessing patient satisfaction, dentist satisfaction, and upper denture peak retention force. Materials & Methods: This research employed a within-subject comparison of two distinct denture kinds in a randomized clinical trial design as follows; group I: CAD/CAM neutral-zone dentures, and group II: heat-polymerized conventional dentures. Twelve completely edentulous patients exhibiting marked ridge resorption were recruited, and each patient received two denture sets in a random sequence. Dentures were clinically evaluated on the insertion day by a non-operating dentist then, patients used their dentures for eight weeks before further assessments. Dentures' clinical adequacy was rated by the dentist via the visual analog scale (VAS), also a digital force gauge was used to measure the dentures' peak retention force. Patient satisfaction was evaluated according to the patient denture assessment questionnaire (PDA). The obtained scores were used to compare the two denture types using the independent-samples t-test and the Pearson's correlation coefficient test was used to assess the degree of association between patient and dentist-reported outcomes. Results: The independent t-test revealed significantly higher values for patient and dentist satisfaction with neutral-zone dentures compared to conventional dentures, and also a higher mean value for CAD/CAM dentures' peak retention force (P <0.001). Pearson's correlation coefficient test revealed a non-significant correlation between patient and dentist satisfaction scores (p>0.05). Conclusion: Milled neutral-zone dentures demonstrated better retention and better impact on patient and dentist acceptance than conventional heat-polymerized dentures.