The aim of this study was to evaluate the effect of the design (extension and adaptation) of a mandibular complete acrylic denture and the use of denture adhesives using a novel in-vitro edentulous model. The model is a highly anatomically accurate replica based on a moderately resorbed human mandibular edentulous arch. The model has been designed and fabricated by means of an elaborate clinical and technical process that employs synthetic elastomeric materials with properties that attempts to reproduce in-vitro characteristics of the soft tissues overlying the ridges and immediate reflected tissues. This model was used to measure and compare the retention of mandibular dentures ofvarying designs (well-fitting, over- and under-extended) with and without the aid of denture fixatives. Retention tests were conducted with different volumes of artificial saliva at a cross head speed of 50 mm/min with 4 equidistant holding points on the denture occlusal surface, using a universal tensile testing machine in an axial pull direction. The effect of three denture adhesives on denture retention was also tested on the same denture types at different times over a period of 5 hours and beyond. The in-vitro model presented can be effectively used to test the retention of mandibular complete dentures. The speed of dislodgement force and amount of saliva are important variables in mandibular denture retention. The retention of well-fitting dentures was statistically higher than that of ill-fitting dentures. A significantly higher retention force was needed to dislodge mandibular dentures (well and ill-fitting dentures) when using a denture adhesive.