Purpose: This investigation was designed to determine whether heat pressing and/or simulated heat treatments affect the flexure strength and microstructure of the lithium disilicate glass-ceramic of the IPS Empress 2 system. Materials and Methods: Four groups of the lithium disilicate glass-ceramic were prepared as follows: group 1 = as-received material; group 2 = heat-pressed material; group 3 = heat-pressed and simulated initial heat-treated material; and group 4 = heat-pressed and simulated heat-treated material with full firings for a final restoration. Three-point bending tests and scanning electron microscopy (SEM) analysis were conducted. Results: The flexure strength of group 2 was significantly higher than that of group 1. However, there were no significant differences in strength among groups 2, 3, and 4, or between groups 1 and 4. The SEM micrographs of the lithium disilicate glass-ceramic showed a closely packed, multidirectionally interlocking microstructure of numerous lithium disilicate crystals protruding from the glass matrix. The crystals in the glass matrix of the heat-pressed materials (groups 2, 3, and 4) were a little more homogeneous and about 2 times bigger than those of the as-received material (group 1). These changes of the microstructure were greatest between groups 1 and 2. However, there were no marked differences among groups 2, 3, and 4. Conclusion: Although there were significant increases in the strength and some changes of the microstructure after the heat-pressing operation, the combination of heat pressing and simulated subsequent heat treatments did not produce an increase of strength of IPS Empress 2 glass-ceramic.