This study compared the fracture strength of single lithium disilicate implant-supported crowns fabricated on two-piece abutments with various materials: ceramic-reinforced PEEK, zirconia, and lithium disilicate. Thirty-six implants were embedded in acrylic cylinders. A two-piece abutment and a crown were designed following a pre-operation scan for a maxillary left central incisor. The designed crown was used to fabricate 36 lithium disilicate crowns. The designed abutment was used to manufacture 36 abutments from 3 materials, 12 each: (A) zirconia; (B) lithium disilicate; and (C) ceramic-reinforced PEEK. Abutments were surface treated and bonded on the titanium base abutments with resin cement. Then, lithium disilicate crowns were bonded on the assigned abutments. Specimens were then subjected to dynamic loading for 1,200,000 cycles. The fracture strength (N) of the assembly was assessed using a universal testing machine. One-way ANOVA followed by multiple comparison tests was used to evaluate the effect of abutment material on the fracture strength of single implant-supported restorations at a significance of .05. The average fracture strength for the groups with zirconia, PEEK, and lithium disilicate two-piece abutments were 1362N ± 218N, 1235N ± 115N, and 1472N ± 171N, respectively. There was a significant (p < 0.05) difference in fracture strength among the groups. The lithium disilicate group had significantly higher fracture strength (p = 0.0058) than the group with PEEK; however, there was no significant (p > 0.05) difference between the other groups. Two-piece abutments restored with lithium disilicate crowns investigated in the study have the potential to withstand the average physiological occlusal forces in the anterior region.