Objective: To evaluate the clinical performance of zirconia-veneered crowns after different surface treatment of zirconia frameworks named as; no surface treatment, sandblasting, silicatization (CoJetTM sand) , Selective infiltration etching (SIE) and the novel acids mixture.Materials and methods: A total of 50 patients of age ranged from 20 to 35 years were presented with root canal-treated molar teeth that needed post-retained restorative treatment. They were divided into 5 groups according to surface treatment of zirconia frameworks (10cases each); Group S1: Zirconia frameworks received no surface treatment. Group S2: Zirconia frameworks received sandblasting with 110µm aluminum oxide airborne particle abrasives.GroupS3: Zirconia frameworks received CoJet sand surface treatment. Group S4: Zirconia frameworks received selective infiltration etching surface treatment. Group S5: Zirconia frameworks received a specially formulated mixture of hydrofluoric acid (HF 9 wt%) and nitric acid (HNO3 26 wt%) at a ratio of (4:1) for 5 min. All Zirconia frameworks received IPS e.max Ceram veneering porcelain. They received all ceramic zirconia based single crowns using Cerec in-Lab CAD/CAM technology for designing and milling zirconia frameworks. Teeth preparation was performed to achieve 2mm occlusal clearance, 1.5mm axial reduction and 1mm rounded shoulder subgingival finish line. Secondary impression was taken for each case using addition silicone rubber base impression material and poured using special reflective cerec stone (CAM Base) to facilitate scanning of the preparation using the in-Lab extra oral scanner “inEos”. 3D virtual models were obtained that were used for designing zirconia frameworks. Then, milling of zirconia blocks were performed using inLab Cerec 3 milling machine to obtain zirconia frameworks followed by sintering procedures for the zirconia frameworks. After try in of sintered zirconia frameworks in the patient’s mouth, they received different types of surface treatment. After that, porcelain build up was conducted by layering technique. All ceramic zirconia based crowns were then cemented using dual-cured resin cement (Multilink Auto Mix) and were subjected to a period of 6, 12, 18, 24 and 30 months clinical observation according to the modified USPHS criteria for indirect restorations, where prosthodontic results were recorded. Statistical analysis was performed using a commercially available software program (SPSS 19; SPSS, Chicago, IL, USA). Values were presented as number and percentages. Chi square test was used to compare categorical data.The level of significance was set at P < 0.05. Results: It was found that at 6 months, score A was recorded in all specimens of IPS e.max Ceram, with no statistically significant difference between different surface treatments (p=1). At 12 months, score A was recorded in all specimens, with no statistically significant difference between different surface treatments (p=1). At 18 months, score A was recorded in 100% specimens of CoJet and acid mixture surface treatment, in 90% of specimens of no treatment and in 80% of specimens of sandblasting and SIE; with no statistically significant difference between different surface treatments (p=0.815). At 24 months, score A was recorded in 80% specimens of sandblasting, CoJet and acid mixture surface treatment, in 66.7% of specimens of no treatment and in 22.2% of SIE; with a statistically significant difference between different surface treatments (p=0.045). At 30 months, score A was recorded in 80% specimens of sandblasting, 88.9% CoJet and 77.8% of acid mixture surface treatment, in 44.5% of specimens of no treatment and in 11.1% of SIE; with a statistically significant difference between different surface treatments (p=0.0024). Conclusions: (1) In all cases, the tested systems showed chipping of the comparable low-strength veneering ceramic but no fracture of the high-strength core or the natural tooth in clinical cases. (2) The treatment of the surface zirconia framework with Cojet system was able to maintain acceptable clinical performance at 24 months and 30 months recall periods. However, the other surface treatments showed lesser performance. (3)No direct correlation between zirconia framework surface treatments and long term bonding to veneering ceramic could be addressed; however, it could be multifactorial such as lack of proper framework support, internal defects, direction, magnitude and frequency of the applied load as well as the residual stresses induced by processing.