This experiment investigated the ability of tooth-colored mineral trioxide aggregate (MTA) to maintain an apical seal in the presence of bacteria when contaminated with blood, saline or saliva. Ninety extracted human teeth with single canals were randomly placed into six groups of 15. Canals were prepared to size 50. The apical 3 mm of each root was removed and 3 mm root-end preparations were made with a #329 bur. Root-end preparations in groups 1 through 3 were filled with MTA after contamination with blood, saline, or saliva, respectively. In group 4, uncontaminated root-end preparations were filled with MTA. Groups 5 and 6 served as negative and positive controls. A tube/tooth assembly was utilized to suspend each root end in Trypticase Soy Broth (TSB). The access chambers were filled with Staphylococcus epidermidis. Positive growth over thirty days was demonstrated by turbidity of the TSB. Vitek analysis was used to confirm the presence of S. epidermidis in the positive samples. Data evaluation consisted of a =2 analysis (p < 0.05). Although all experimental groups demonstrated leakage, tooth-colored MTA contaminated with saliva (group 3) leaked significantly more than the uncontaminated tooth-colored MTA (group 4) (p = 0.028).