Background: To compare the loss of preload in absence of loading and after a fixed number of ideal masticatory cycles in two different connection systems using all-on-four prosthetic model. Methods: Two equal models of an edentulous mandible rehabilitated with all-on-four technique with two types of abutment system (MUA and OT-Bridge) supporting a hybrid prosthesis, were used. Initial torque values of the prosthetic fixing screw, after ten minutes from initial screw tightening and after 400000 masticatory cycles were registered using a mechanical torque gauge. Differences between initial and final torque values were reported for each anchoring system and the two systems were finally compared. Results: No statistically significant differences regarding the loss of preload between MUA and OT-Bridge system were found after 400000 masticatory cycles; however, in MUA system it was found between anterior and posterior implant screws. A significant difference in preload loss was found only for MUA system comparing the initial screw torque to that measured after 10 minutes from the tightening in absence of cyclic loadings. Conclusions: MUA and OT-Bridge are reliable prosthetic anchoring systems able to tolerate repeated masticatory cycles also on distal cantilever in all-on-four rehabilitation model without any significant loss of preload in screw tightening