Fiber-reinforced composite (FRC) fixed partial dentures (FPD) have become an accepted part of the restorative dentist's armamentarium. The aim of this study was to evaluate in vitro the influence of retainer design on the strength of two-unit cantilever resin-bonded glass FRC-FPDs. Four retainer designs were tested: a dual wing, a dual wing + horizontal groove, a dual wing + occlusal rest and a step-box. Of each design on 7 human mandibular molars, FRC-FPDs of a premolar size were produced. The FRC framework was made of resin Revolution (Kerr) impregnated glass fibers (GlasSpan, GlasSpan) and veneered with hybrid resin composite (Charisma, Kulzer). Revolution (Kerr) was used as resin luting cement. FRC-FPDs were loaded to failure in a universal testing machine. T (Student's)-test was used to evaluate the data. The four designs were analyzed with finite element analysis (FEA) to reveal the stress distribution within the tooth/restoration complex. Significantly lower fracture strengths were observed with inlay-retained FPDs (step-box: 172±11 N) compared to wing-retained FPDs (p<0.05) (a dual wing + horizontal groove 222±9 N). The highest fracture strengths were observed with dual wing + occlusal rest FPDs: 250±10 N compared to inlay-retained FPDs (p<0.001) and wing-retained FPDs (p<0.001). FEA showed more favorable stress distributions within the tooth/restoration complex for dual wing retainers+ occlusal rest FPDs. There was stress concentration around connectors and retainers near connectors. A dual-wing retainer with occlusal rest is the optimal design for replacement of a single premolar by means of a two-unit cantilever FRC-FPDs.