The present study elucidates the mechanical performance of different designs of resin-bonded fixed dental prostheses made of lithium disilicate simulating masticatory loads of anterior or canine guidance. A three-dimensional model of maxilla was constructed containing central incisor and canine teeth, with edentulous space of the lateral incisor. Three designs of prosthesis were created: retained in central incisor (1-I), retained in canine (1-C) and fixed in both teeth (2-IC). The computational analysis was performed for load in canine and central incisor separately (100N, 45°). The tensile and shear stresses were calculated for the resin-bonded fixed dental prosthesis, bonding surface of each retainer and cement layer using 3D finite element analysis. The 20 highest stress values were analyzed using two-way ANOVA and post-hoc Tukey test, all with α = 5%. The computational analysis showed that 2-retainer resin-bonded fixed dental prosthesis presented the worst prognosis regardless of the mandibular movement. ANOVA showed that Mandibular movement*Retainer interaction influenced on the tensile and shear stresses values (p < 0.01). Higher stresses were observed in the connector region for all groups (13-82.2 MPa; 11-70.2 MPa). In order to reduce the stress concentration in the resin-bonded fixed dental prosthesis and the retainer made of lithium disilicate, the occlusion may serve as the selection criteria of the unitary abutment for better sustainability.