This study assessed the effect of different surface conditioning methods and ageing protocols on adhesion of resin cement to hybrid ceramic and polymeric CAD/CAM materials. CAD/CAM materials (n = 360, n = 30 per group), namely (a) Lithium disilicate (IPS e.max CAD-LIS), (b) Zirconia (IPS e.max ZirCAD-ZIR), (c) Polymer (Lava Ultimate-LAV), (d) Polymer infiltrated ceramic network (Enamic-ENA), (e) Polymer infiltrated ceramic (Experimental-1-CS1), (f) Polymer infiltrated ceramic (Experimental-2-CS2), (g) Lithium disilicate reinforced alumina (n!ce-NIC) were cut into slices (3 x 6 x 8 mm(3)) and conditioned: (a) Method 1: 5% hydrofluoric acid etching (H)+silane and (b) Method 2: Silica coating (CoJet (A)+silane). Group LIS was conditioned with only Method 1 and Group ZIR only with Method 2 (control). Resin cement (Variolink Esthetic II) was bonded onto the conditioned specimens and photopolymerized. One-half of the specimens was subjected to ageing (thermocycling 5-55 degrees, 5000 cycles) and the other half was stored in distilled water (37 degrees C, 24 h). The resin-substrate interface was loaded under shear forces in a Universal Testing Machine (1 mm/min). Data (MPa) were analyzed using two-way ANOVA and Tukey`s tests (alpha = 0.05). Substrate type, conditioning method and ageing had a significant effect on adhesion values (p < .05). In aged conditions, ENA-H, ENA-A, LAV-H, LAV-A, CS2-A (15 +/- 4 - 11.6 +/- 5) showed no significant difference (p > .05), with the CS2-A (15 +/- 4) showing the least reduction (5.5%) compared to all other groups (5.8-62.6%). CS1-A (100%) followed by ENA-H, ENA-A (93%), CS2-A (80%) presented the highest incidence of cohesive failures after ageing.