Purpose: 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 fiber-reinforced composite (FRC) fixed dental prostheses (FDP). Materials and Methods: Four retainer designs were tested: a proximal box, a step-box, a dual wing, and a step-box-wing. Of each design on 8 human mandibular molars, FRC-FDPs of a premolar size were produced. The FRC framework was made of resin impregnated unidirectional glass fibers (Estenia C&B EG Fiber, Kuraray) and veneered with hybrid resin composite (Estenia C&B, Kuraray). Panavia F 2.0 (Kuraray) was used as resin luting cement. FRC-FDPs were loaded to failure in a universal testing machine. One-way ANOVA and Tukey's post-hoc test were 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. Results: Significantly lower fracture strengths were observed with inlay-retained FDPs (proximal box: 300 ± 65 N; stepbox: 309 ± 37 N) compared to wing-retained FDPs (p 0.05) (step-box-wing: 662 ± 99 N; dual wing: 697 ± 67 N). Proximal- box-, step-box-, and step-box-wing-retained FDPs mainly failed with catastrophic cusp fracture (proximal box 100%, step-box 100%, and step-box-wing 75%), while dual-wing-retained FDPs mainly failed at the adhesive interface and/or due to pontic failure (75%). FEA showed more favorable stress distributions within the tooth/restoration complex for dual wing retainers. Conclusion: A dual-wing retainer is the optimal design for replacement of a single premolar by means of a two-unit cantilever FRC-FDPs. Keywords: fiber-reinforced composite, cantilever, fixed dental prosthesis, static fracture strength, finite element analysis