Purpose: The mastoid region is ideal for studying sexual dimorphism due to its anatomical position at the base of the skull. This study aimed to determine sex in the Iranian population based on measurements of the mastoid process using different data mining algorithms. Materials and Methods: This retrospective study was conducted on 190 3-dimensional cone-beam computed tomographic (CBCT) images of 105 women and 85 men between the ages of 18 and 70 years. On each CBCT scan, the following 9 landmarks were measured: the distance between the porion and the mastoidale; the mastoid length, height, and width; the distance between the mastoidale and the mastoid incision; the intermastoid distance (IMD); the distance between the lowest point of the mastoid triangle and the most prominent convex surface of the mastoid (MF); the distance between the most prominent convex mastoid point (IMSLD); and the intersecting angle drawn from the most prominent right and left mastoid point (MMCA). Several predictive models were constructed and their accuracy was compared using cross-validation. Results: The results of the t-test revealed a statistically significant difference between the sexes in all variables except MF and MMCA. The random forest model, with an accuracy of 97.0%, had the best performance in predicting sex. The IMSLD and IMD made the largest contributions to predicting sex, while the MMCA variable had the least significant role. Conclusion These results show the possibility of developing an accurate tool using data mining algorithms for sex determination in the forensic framework.