This study aimed to clarify the effects of multiple firings on the translucency, crystal structure, and mechanical strength of highly translucent zirconia. Four types of highly translucent zirconia (LAVA Esthetic, LAVA Plus, KATANA Zirconia STML, and KATANA Zirconia HTML) were fired three times at three different temperatures, and the translucency, crystal structure, and flexural strength were evaluated before and after firing. The translucency was statistically compared using repeated-measures analysis of variance; the zirconia phase composition was assessed using X-ray diffraction followed by Rietveld analysis; and the biaxial flexural strength was assessed using Weibull analysis. The translucency of LAVA Esthetic and KATANA Zirconia HTML decreased significantly after firing, and the crystal composition of LAVA Plus and KATANA Zirconia HTML changed after multiple firings, whereas multiple firings did not affect the biaxial flexural strength of any samples. Thus, multiple firings may affect the optical properties of highly translucent zirconia.