INTRODUCTION: Sealing ability is an important factor for a root-end filling material in endodontic surgeries. This in vitro study aimed to compare the sealing ability of mineral trioxide aggregate (MTA) and a new endodontic cement named calcium enriched mixture (CEM) cement as root-end filling materials. MATERIALS AND METHODS: The experiments were carried out in dry, saliva or blood contaminated root-end cavities of hundred single-rooted extracted human teeth. After decoronation, the root canals were cleaned, shaped, obturated, and stored in 100% humidity for 5 days. Removing the apical 2-3mm of each root, a 3mm deep root-end cavity was ultrasonically prepared. Samples were randomly divided into 2 test groups of 45 roots/experimental material, and one subgroup (n=15) for each environmental condition as follows; a) dried before placing the filling material, b) filled after contamination with saliva, and c) filled after contamination with blood. Ten roots were used as positive/negative controls. Samples were placed in an incubator at 37°C for a day and immersed in methylene blue dye under reduced pressure environment for 48hours. Roots were sectioned longitudinally and examined under stereomicroscope by an independent observer. RESULTS: Using Kruskal-Wallis and Mann-Whitney U tests with Bonferroni correction, the results demonstrated significantly less leakage for the CEM cement in saliva contaminated condition when compared to MTA (P<0.001). CONCLUSION: It can be concluded that the sealing ability of CEM cement was superior to MTA in saliva contaminated condition.