OBJECTIVE: The aim of this in-vitro study is to assess the effect of cyclic loading fatigue on failure load of CAD/CAM cement-retained implant crowns and screw-retained implant crowns with screw access holes sealed with composite or Enamic inlay. MATERIALS AND METHODS: For the screw-retained implant crowns, Ivoclar e.max and Vita Enamic CAD/CAM (n=44 for each material) and Enamic inlays (n=44) were designed using Sirona in-Lab software system (SW4 4.2.5) and milled using CEREC in-Lab MC XL. All the prepared e.max and Enamic crowns were cemented to Sirona TiBase (B O 4.1 L) using Ivoclar hybrid multilink cement. The access holes were sealed either by using composite or and Enamic inlay (n=22 for each group). For cement-retained implant crowns, Ivoclar e.max, Vita Enamic, and Vita Mark II CAD/CAM (n=20 for each material) and Enamic and Zirconia abutments (n=40 for each group) were designed using Sirona in-Lab software system (SW4 4.2.5) and milled using CEREC in-Lab MC XL. All the prepared zirconia and Enamic abutments were cemented to Sirona TiBase (B O 4.1 L) using Ivoclar hybrid multilink cement. Then, all prepared Ivoclar e.max, Vita Enamic, and Vita Mark II crowns were cemented to the abutments using Multilink Automix cement. After cementation, 10-12 specimens from each group (both screw and cement-retained) were subjected to a static load to failure test in a universal mechanical testing machine (Instron 5566A). The mean failure load for each group was calculated. The other 10 specimens for each group were subjected to cyclic loading fatigue under 40% of static failure load for 50,000 and 100,000 cycles. After cyclic loading, the surviving specimens were tested for static failure load. The comparison of failure load between tested groups was analyzed by one-way ANOVA using JMP Pro 13 with α=0.05. RESULTS: For IPS e-max CAD screw-retained implant crowns, there was a significant difference in the failure load at static and after cyclic fatigue for 50,000 cycles, but no significant difference between static and after cyclic fatigue for 100,000 cycles. For Vita Enamic crowns, there was no significant difference in the failure load at static and after cyclic fatigue for 50,000 cycles and 100,000 cycles. There was a significant difference in the failure load between screw-retained implant crowns sealed with composite and those sealed with Enamic inlay. For IPS e-max CAD /Zr abutment and Vita Mark II/ Enamic abutment cement-retained implant crowns, there was a significant difference in the failure load at static and after cyclic fatigue for 100,000 cycles. For Vita Enamic /Zr abutment cement-retained implant crowns, there was no significant difference in the failure load at static and after cyclic fatigue for 100,000 cycles. CONCLUSION: The screw-retained implant crowns sealed with composite had higher failure load than those sealed with Enamic inlay. The cyclic fatigue has an effect on IPS e.max CAD screw-retained implant crowns, IPS e-max CAD /Zr abutment and Vita Mark II/ Enamic abutment cement-retained implant crowns. The cyclic fatigue has no effect on Vita Enamic screw-retained implant crowns and Vita Enamic/ Zr abutment cement-retained implant crowns.