Understanding the mechanical behavior of the arterial wall and its spatial variations is essential for the study of vascular physiopathology and the design of biomedical devices that interact with the arterial wall. Although it is generally accepted that the aortic wall gets stiffer along its length, the spatial variations in the mechanical behavior of the thoracic aorta are not well understood. In this study, therefore, we investigate both longitudinal and circumferential variations in the mechanical properties of the porcine descending thoracic aorta. Using a previously developed experimental method and stress–strain analysis, the stress, stretch, tangent modulus (TM), and pressure–strain elastic modulus (PSEM) are estimated in the range of in vivo pressure. The results show that the longitudinal differences of both TM and PSEM are statistically significant in the posterior region but not in the anterior region. Both moduli are greater in the posterior distal region when compared with the other test regions. The findings of this study meet a need for clarifying the region investigated, especially in circumferential region, to study the regional variations in biomechanics of blood vessels. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.