Objective: The objective of this study was to quantify the potential effects of screw- and cement-retention on strain development of implant-supported fixed dental prostheses (FDPs). Method and Materials: A total of 20 single crowns and 70 three-unit FDPs were fabricated to fit an in vitro model situation with two implants. Using strain gauges attached to the model material adjacent to the implants, strain development of the restorations during fixation was recorded while the parameters cement type (provisional and definitive cement), cementation force (10 N and 100 N), and tightening torque (5 Ncm, 10 Ncm, and 15 Ncm) were varied. MANOVA with Pillai's trace was used for pairwise comparisons between groups (α = .05). Results: Mean absolute strain development ranged from 5.11 µm/m for to 27.26 µm/m for single crowns and from 16.46 µm/m to 689.04 µm/m for multi-unit restorations. Screw-retained single crowns exhibited significantly smaller strain development as compared to cement-retained single crowns (P = .009). The type of cement used seemed to have no effect on strain development of an FDP regardless of the cementation force applied (P = .064 and P = .605). An increase in tightening torque for screw-retained FDPs also had no effect on resulting strain development (P values ranging from .692 to .807). Nonuniform results were found when comparing screw- and cementretention as the retention mechanism for FDPs. Conclusion: Strain development seems to depend predominantly on the accuracy achieved during the fabrication process whereas the retention mechanisms themselves as well as their potential parameters only have a minor effect. Keywords: cement-retention, implant-supported dental prosthesis, passive fit, screw-retention, stress development