Objective: As the high strength glass ceramics had attained a profound contribution in prosthodontics, it was aimed to evaluate the fatigue performance of two machinable high strength glass ceramics with further fracture mode analysis. Materials and methods: Twenty crowns were fabricated using Cerec in-Lab CAD\CAM system, ten crowns were fabricated from IPS. E.max CAD: group (EM-LDS) as control group and ten crowns were fabricated from VITA SUPRINITY: group (VS-ZLS). The completed crowns were cemented on epoxy resin dies. The cemented crowns were subjected to thermomechanical cycling for 75000 cycles, then loaded until fracture by using universal testing machine. Failure mode were assesses guided by Brukes' classification for all specimens. The collected data was statistically analyzed using Student t-test and Paired t-test while the significance level was set at P ≤ 0.05, in addition to descriptive statistics of the fracture mode analysis. Results: There was no statistically significant difference in fatigue performance between the two tested groups with the major fracture occurrence in type III central fracture. Conclusion: both tested high strength glass ceramics are considered as acceptable modalities for restoration of single tooth restoration as both materials have comparable strength and exceeded the reported range of human masticatory forces.