© 2017 The Academy of Dental Materials Objective Denture adhesives are widely used to avoid the detachment and sliding of dentures. However, the adhesion properties can be affected by variation in mouth conditions such as the level of salivation. The objective of this study was to understand the effect of environmental conditions on the adhesion properties of a commercially available denture adhesive named as Poligrip®Free manufactured by GlaxoSmithKline Ltd., UK and to identify the reasons for the observed variation in its adhesion strength. Methods The failure mechanisms of denture adhesive have been assessed through using different physical, mechanical and thermal characterization experiments. All methods were used in different pH, temperatures, and salivation conditions and at the end, a strategy was proposed to overcome the failure of the paste in hyposalivation as well. Results In vitro models mimicking the denture gingival interface were designed to evaluate the adhesion properties of the investigated adhesive. Changes in the adhesion strength in response to three major factors related to the oral conditions including level of salivation, pH, and temperature were measured. The results of lap shear, tensile test, and internal interactions suggested a cohesion failure, where the lowest adhesion strength was due to hyposalivation. Fourier transform infrared spectroscopy (FTIR) and rheological analysis confirmed the importance of hydrogen bonds and hydration in the adhesion strength of the paste. Significance The investigated scenarios are widely observed in patient using denture adhesives and the clinical reports have indicated the inconsistency in adhesion strength of the commercial products. After identifying the potential reasons for such behavior, methods such as the addition of tripropylene glycol methyl ether (TPME) to enhance internal hydrogen bonds between the polymers are proposed to improve adhesion in the hyposalivation scenario.