Aim: To evaluate the changes in the temperature of zirconia during grinding under different clinical conditions. Materials and Methods: A total of 60 zirconia framework specimens were fabricated and divided into groups of 10 specimens each. Two different handpieces, namely, a high-speed handpiece (HSH) and a low-speed handpiece (LSH), were used for grinding with and without water cooling. Fine- and coarse-grit diamond burrs were used with the HSH, separately. The following six groups were created: (a) HSH fine-grit with water cooling, (b) HSH coarse grit with water cooling, (c) HSH fine grit without water cooling, (d) HSH coarse grit without water cooling, (e) LSH with water cooling, and (f) LSH without water cooling. Each zirconia framework was ground until 1 mm3 of the material was removed. Temperature values corresponding to the grinding techniques were compared and statistically analyzed. One-way analysis of variance was used to compare the group parameters, while the Tukey honest significant difference test was used to detect significant differences between the groups. The significance level was set at P <.05. Results: The highest mean temperature was measured in the case of grinding with the LSH without water cooling (54.7 °C ± 11.6 °C), while the lowest mean temperature was observed in the case of grinding with the HSH using the coarse-grit diamond rotary instrument under water cooling (22.6 °C ± 0.6 °C). Conclusions: The grinding of zirconia must be performed with an HSH under water cooling. Further, when water cooling is used, neither the type of handpiece nor the grain type of the rotary instrument used as it has a significant effect on the temperature.