The aim of this invitro study was to evaluate the fracture resistance of endodontically treated canines restored with one-piece milled zirconia post and core in the varying ferrule modes. Fifty recently extracted human maxillary canines were endodontically treated and randomly divided into 5 groups of 10 specimens each. According to the defect degree of ferrule, intact ferrule was classified as group A and served as control, 2 mm ferrule height without buccal ferrule was classified as group B, 2 mm ferrule height without mesial and buccal ferrule was classified as group C, 2 mm ferrule height without mesial, buccal and lingual ferrule was classified as group D, no ferrule preparation was classified as group E. All of the teeth were restored with one-piece milled zirconia post and core, and zirconia crowns. The teeth were prepared to standardized specifications. The restored teeth were loaded to fracture at a 135° angle to their long axis, at a cross-head speed 0.5 mm/min, and the load (N) at failure was recorded. Statistical analysis was performed by SNK pairwise multiple comparisons (α=0.05). The mean fracture resistance of five groups as follows: 1019.30±139.01N for group A, 861.20±105.67N for group B, 833.70±100.56N for group C, 733.20±96.91N for group D, 698.00±99.90N for group E. The fracture resistance of restored teeth between group B and group C, group D and group E had no statistically significant difference(P>0.05). The fracture resistance of the rest pairwise group comparisons had statistically significant difference(P<0.05). Increasing the absence degree of ferrule, it was found that the fracture resistance decrease. The buccal and lingual ferrule were more important than mesial ferrule for enhanced fracture resistance. This in vitro study supports evidence that reserving the buccal and lingual ferrule is a key point to increase the fracture resistance of canines restored with one-piece milled zirconia post and core.