To evaluate the fracture resistance of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate mandibular posterior crowns with virgilite of different occlusal thicknesses and compare them to traditional lithium disilicate crowns. Seventy-five chairside CAD-CAM crowns were fabricated for mandibular right first molars, 60 from novel lithium disilicate with virgilite (CEREC Tessera, Dentsply Sirona), and 15 from traditional lithium disilicate (e.max CAD, Ivoclar Vivadent). These crowns were distributed across five groups based on occlusal thickness and material: Group 1 featured CEREC Tessera crowns with 0.8mm thickness, Group 2 had 1.0mm thickness, Group 3 had 1.2mm thickness, Group 4 with 1.5mm thickness, and Group 5 included e.max CAD crowns with 1.0mm thickness. These crowns were luted onto 3D-printed resin dies using Multilink Automix resin cement (Ivoclar Vivadent). Subsequently, they underwent cyclic loading (2,000,000 cycles at 1Hz with a 275 N force) and loading until fracture. Scanning electron microscopy (SEM) assessed the fractured specimens. Statistical analysis involved one-way ANOVA and the Kruskal-Wallis Test (α = 0.05). Fracture resistance varied significantly (<0.001) across mandibular molar crowns fabricated from chairside CAD-CAM lithium disilicate containing virgilite, particularly between crowns with 0.8mm and those with 1.2 and 1.5mm occlusal thickness. However, no significant differences were found when comparing crowns with 1, 1.2, and 1.5mm thicknesses. CEREC Tessera crowns with 1.5mm thickness exhibited the highest resistance (2119N/mm2), followed by those with 1.2mm (1982N/mm2), 1.0mm (1763N/mm2), and 0.8mm (1144N/mm2) thickness, whereas e.max CAD crowns with 1.0mm occlusal thickness displayed the lowest resistance (814N/mm2). The relationship between thickness and fracture resistance in the virgilite lithium disilicate full-coverage crowns was directly proportional, indicating that increased thickness corresponded to higher fracture resistance. No significant differences were noted among crowns with thicknesses ranging from 1 to 1.5mm. This novel ceramic exhibited superior fracture resistance compared to traditional lithium disilicate.