Aim: To evaluate in vitro the effect of apical root canal perforation size on push-out bond strength of glass fiber dowels cemented to sound or perforated root canals using two different adhesive systems. Materials and materials: A total of 120 human-extracted intact upper central incisors were selected. Teeth were sectioned 3 mm coronal to cement enamel junction, and the remaining root received endodontic root canal therapy. The roots were divided into two experimental groups according to the root condition: either sound (n = 40) or apically perforated (n = 80). Dowel spaces were prepared for all specimens to a depth of 10 mm. Roots were restored with glass fiber dowels. The experimental group was further subdivided into four subgroups (n = 20) according to the adhesive system used and apical perforation size: group I, perforated root 2 mm apically, dowel cemented using total-etch adhesive cement; group II, perforated root 2 mm apically, dowel cemented using self-etch adhesive cement; group III, perforated root 4 mm apically, dowel cemented using total-etch adhesive cement; and group IV, perforated root 4 mm apically, dowel cemented using self-etch adhesive cement. The control group, sound root, was divided into two subgroups: group I, sound root, dowel cemented using total-etch adhesive cement, and group II, sound root, dowel cemented using self-etch or total-etch adhesive cement. Each root was then cut horizontally, and root segments were prepared to be tested. The bond strength between dowel and dentin was measured with universal testing machine using a push-out test. The two-way analysis of variance (ANOVA) was used to analyze the data and post hoc Tukey's test (α = 0.05). Results: Root canal perforation and the type of adhesive system used resulted in significant differences in push-out bond strength (p < 0.05). Regardless of root canal perforation size, glass fiber dowels in normal root canals had significantly higher mean bond strength values (9.2 ± 1.4 MPa) compared with perforated root canals (6.1 ± 1.4 MPa). Also, self-etch protocol had significantly higher mean bond strength values (9.1 ± 1.3 MPa) compared with total-etch protocol (6.2 ± 2.1 MPa). Conclusion: The apical root perforation size caused a direct effect on the bond strength of the glass fiber dowels cemented to dentin by reducing the bond strength values to the root dentin regardless of the adhesive system used. Clinical significance: Prior to perforation repair, dentist or endodontist should evaluate the perforation size to predict the treatment outcome.