AIM: Surface treatment is necessarily required for bonding of zirconia to the veneering porcelain and luting cements. Sandblasting is the most common and probably the most efficient surface treatment method. Sandblasting roughens the surface and may affect the flexural strength of zirconia. Different sandblasting protocols may yield variable results. This study sought to assess the effect of sandblasting angle and distance on the biaxial flexural strength of zirconia-based ceramics. MATERIALS AND METHODS: This in vitro experimental study was conducted on 50 zirconia discs measuring 1.2 ± 0.2 mm in thickness and 15 ± 0.2 mm in diameter, which were randomly divided into five groups (n = 10) of one control and four experimental groups subjected to sandblasting with 110 µm aluminum oxide particles under 2 bar pressure for 10 seconds at 15 and 25 mm distances and 45 and 90° angles (between the nozzle head and zirconia surface). Surface roughness was measured by a roughness tester and samples were subjected to thermocycling followed by biaxial flexural strength testing according to ISO6872. The data were analyzed using one-way analysis of variance (p < 0.05). RESULTS: No statistically significant difference was noted in the mean biaxial flexural strength of the five groups (p = 0.40). Different sandblasting protocols yielded significantly different surface roughness values (p < 0.001). The highest and the lowest mean surface roughness belonged to 15 mm/90° (0.51 µm) and control (0.001 µm) groups respectively. CONCLUSION: Change in sandblasting angle and distance had no significant effect on the biaxial flexural strength of zirconia-based ceramic, but surface roughness was significantly different in the study groups. Clinical significances: Regardless of sandblasting angle, increasing distance to 25 mm significantly decreases surface roughness that may negatively affect zirconia bond strength.