Peripheral Artery Disease (PAD) is a significant manifestation of cardiovascular disease, often remaining undiagnosed due to asymptomatic presentation. This study employs computational modeling to better understand blood hemodynamics in PAD, focusing on the femoral artery. Comparison between Computational Fluid Dynamics (CFD) and Fluid–Structure Interaction (FSI) methods to simulate blood flow and arterial wall interactions were used to analyze the differences of predicted blood hemodynamics. An idealized model of the common femoral artery (CFA) with branches superficial femoral artery (SFA) and profunda femoral artery (PFA) was constructed based on published clinical data. Both CFD and FSI simulations were performed using ANSYS software, with blood modeled as a Newtonian fluid and the arterial wall as a linear elastic material. Results show that while both methods capture similar overall flow patterns, FSI reveals more complex velocity profiles and localized variations, particularly at the bifurcation. Analysis of Time-Averaged Wall Shear Stress (TAWSS) distributions indicates that CFD predicts a 2.41% greater surface area of low TAWSS (< 0.4 Pa) compared to FSI, suggesting potential overestimation of plaque formation risk. These findings highlight the importance of incorporating fluid–structure interactions in vascular modeling for more accurate hemodynamic stress predictions, which could improve PAD diagnosis and intervention strategies.