Purpose: The aim of this study was to compare the efficacy of two denture adhesives in edentulous patients wearing complete maxillary and mandibular dentures. Materials and Methods: Twenty-four edentulous patients were treated with complete dentures following a standardized protocol. Resistance to dislodgement of both dentures was measured in simulated functional movements by means of a gnathometer and a dynamometer. These outcome measurements were assessed first without the adhesive and then after two successive 2-week periods of using a randomly assigned denture adhesive in a crossover experimental design. The adhesives used were a standard one (Kukident Classic) and a new adhesive with a similar formulation but different physical characteristics (Kukident Pro). Results: Twenty-four patients (mean age: 58 years) participated in this study. Gnathometer results demonstrated significant differences between the nonadhesive group and both the experimental adhesive (P = .008) and the control adhesive groups (P = .021). Differences between both adhesive groups were not significant (P = .161). Dynamometer results showed highly significant differences between the maxillary and mandibular dentures in both the nonadhesive group and the two adhesive groups (P ≤ .0001). Similarly, highly significant differences were found when any of the adhesive groups were compared with the nonadhesive group (P = .0001). The patient subjective evaluation was very favorable for both adhesives. Conclusions: This study confirms the predicted and expected improvement in the stability and retention of well-fitting complete dentures with the adjunctive use of adhesives. The observed and recorded improvements with the new adhesive as compared to the traditional one were not statistically significant. Int J Prosthodont 2009;22:361–367.