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Purpose To determine and compare the mechanical properties of 3D-printed yttriastabilized zirconia to milled isostatic pressed yttria-stabilized zirconia, with the following hypotheses: (1) The flexural strength of 3D-printed yttria-stabilized zirconia is comparable to milled yttria-stabilized isostatic pressed zirconia; and (2) thermocycling and chewing simulation do not affect the flexural strength of 3D-printed yttria-stabilized zirconia. Materials and methods A total of 30 bars of an experimental 3D-printed 3 mol% yttriastabilized zirconia (LithaCon 3Y 230, Lithoz) and 10 bars of milled isostatic pressed zirconia (Prettau Zirconia, Zirkonzahn) were utilized. The printed zirconia bars were divided into three groups (n = 10 bars per group): (1) untreated (control); (2) thermocycled; and (3) tested after chewing simulation. A flexural strength test was performed on all samples using a three-point bend test in an Instron Universal testing machine. One-way analysis of variance on ranks was used to compare milled to printed zirconia. The effects of thermocycling and load cycling on 3D-printed zirconia were also determined. Results The flexural strength values for milled and printed zirconia were 936.3 ± 255.0 MPa and 855.4 ± 112.6 MPa, respectively. There was no statistically significant difference in flexural strength between the milled and printed zirconia (P = .178). No statistically significant differences were observed between the control 3D-printed zirconia group and the thermocycled (888.4 ± 59.3 MPa) or load-cycled printed zirconia (789.6 ± 133.8 MPa; P = .119). Conclusion Printed 3 mol% yttria-stabilized zirconia has comparable flexural strength to milled yttria-stabilized isostatic pressed zirconia. The thermocycling and chewing simulation used in this study did not significantly alter the flexural strength of the printed 3 mol% yttria-stabilized zirconia. These results indicate a promising role for 3D printing in the fabrication of zirconia restorations. Additional studies are needed to explore the full potential of this technology.