Introduction: The proximity of the roots of the posterior maxillary teeth to the maxillary sinus is a constant challenge to the dental practitioner. Because the majority of studies have assessed the relationship regarding molars, the present study focused on premolars. Methods: Cone-beam computed tomographic images of 192 patients were reconstructed in sagittal, coronal, and axial planes to quantify the distances between the root apices of the maxillary premolars and the adjacent maxillary sinus. Measurements were taken for each root, and data were correlated with age, sex, side, and presence of both or absence of 1 of the 2 premolars. Results: A total of 296 teeth (177 first and 119 second premolars) were evaluated. The mean distances from buccal roots of the first premolars to the border of the maxillary sinus in the sagittal, coronal, and axial planes ranged from 5.15 AE 2.99 to 8.28 AE 6.27 mm. From palatal roots, the mean distances ranged from 4.20 AE 3.69 to 7.17 AE 6.14 mm. The mean distances of second premolars were markedly shorter in buccal roots between 2.32 AE 2.19 and 3.28 AE 3.17 mm and in palatal roots between 2.68 AE 3.58 and 3.80 AE 3.71 mm, respectively. The frequency of a premolar root protrusion into the maxillary sinus was very low in first premolars (0%-7.2%) but higher in second premolars (2.5%-13.6%). Sex, age, side, and presence/absence of premolars failed to significantly influence the mean distances between premolar roots and the maxillary sinus. Conclusions: Based on the calculated mean distances of the present study, only few premolars (and if so second premolars) would present a risk of violating the border of the maxillary sinus during conventional or surgical endodontic treatment or in case of tooth extraction. (J Endod 2014;40:1541-1548