Aim: The purpose of this study was to evaluate the effect of different die-spacer thicknesses on the retentive strength of all zirconium crowns using self-adhesive resin cement (Relyx Unicem). Materials and method: A total of 24 freshly extracted sound human maxillary first premolar teeth were mounted and then received a standardized preparation for full contour zirconia crown restorations with a deep chamfer finishing line, planner occlusal reduction, 6° overall taper. The teeth were scanned directly using Sirona Omnicam digital intra-oral scanner. Preparations surface areas were measured using Auto CAD architecture software. Teeth were then randomly assigned into 3 main groups according to the die spacer thickness selected during the designing phase by inLab SW 16.1 designing program (n=8): Group A: 80 μm; Group B: 100 μm and Group C: 120 μm. Monolithic zirconia crowns were constructed using Sirona In-Lab MC X5 milling unit. Each group was cemented with Relyx Unicem self-adhesive luting cement. Statistical analyses: The data were statistically analyzed using 1-way ANOVA and Post-hoc Bonferroni test at 0.05 level of significance. Results: The statistical analysis showed that die spacer thickness had a significant effect on the crown retentive stress and the highest mean of retentive stresses was recorded for Group A (7.4 ± 0.7 SD) while Group C recorded the lowest mean of retentive stresses (5.5 ± 0.8 SD). In addition, the predominant mode of failure was type 3 (cement principally on ceramic). Conclusion: Within the limitations of this study, the use of 80 μm spacer thickness resulted in significally higher retention values than 100 μm and 120 μm spacer. In contrast, there was no significant difference in retention between 100 μm and 120 μm.