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The interface pressure is currently the only clinical tool to estimate the risk of sitting-related pressure ulcers. However, it provides little information on the loading condition in deep tissues. We present a comprehensive 3-D finite element (FE) model for human buttocks with the consideration of the joint configuration and realistic boundary conditions in a sitting posture. Sitting induced soft tissue deformation, internal pressure, and von-Mises stress were computed. The FE model was well validated qualitatively using actual displacement obtained from magnetic resonance imaging (MRI) images. FE analysis demonstrated that the deformation induced by sitting pressure was substantially different among muscle, fat, and skin. The deformation of the muscle varied with location and the maximum was seen in the regions underneath the bony prominence of ischial tuberosity. In these regions, the range of compressive pressure was 65-80 kPa, 50-60 kPa, and 55-65 kPa, for skin, fat, and muscle, respectively. The von-Mises stress distribution had a similar pattern. In conclusion, this study suggests a new methodology for the development and validation of FE models for investigating the risk of sitting-related soft tissue injury. The proposed model may provide researchers and therapists with a powerful technique for evaluating the effectiveness of various postural modulations in preventing deep tissue ulcers.