This study evaluated the effect of setting conditions (time and hydration) on mineral trioxide aggregate (MTA) flexural strength. MTA beam specimens were allowed to set for either 24 or 72 hours with specimens exposed to moisture on either one or two specimen surfaces. These moisture conditions were used to simulate MTA setting with only external tissue moisture (one-sided moisture) versus tissue moisture in combination with a moistened intracanal cotton pellet (two-sided moisture). Ten specimens were stored at 37 degrees C under each of the four experimental setting conditions (1) 24-hour/moist/2-sided; (2) 24-hour/moist/1-sided; (3) 72-hour/moist/2-sided; (4) 72-hour/moist/1-sided. After storage at respective setting conditions, MTA specimens were tested to failure with three-point bend test to measure flexural strength. Flexural strength of the 24h/moist/2-sided specimens, 14.27 +/- 1.96 MPa, was significantly higher (p < or = 0.05) than the flexural strength values associated with conditions two, three, and four, respectively, 10.77 +/- 1.44, 11.16 +/- 0.96, 11.18 +/- 0.99 MPa, which were not significantly different from each other (p > 0.05). Clinically, these results suggest that a moistened cotton pellet should be placed on the intracanal MTA surface under a temporary restoration; and if possible, to optimize flexural strength, the moistened pellet should only remain in place for 24 hours.