The design of medical-grade compression garments is essential for therapeutic efficacy, requiring precise pressure distribution on specific body areas. This study evaluates the effectiveness of virtual fit technology, focusing on CLO3D, in designing these garments. Simulated strain and pressure values from CLO3D were compared to experimental measurements, alongside the development of a CP model using CLO3D’s digitized stretch stiffness (Youn’s CP model). Using a 3D-scanned manikin, the mechanical behavior of eight knit fabrics, including composite structures, was assessed under strain of 5%, 10%, 15%, and 20%. The results showed that CLO3D’s built-in pressure simulation overestimated the pressure, especially in plaited fabrics such as SJP and INTP, with discrepancies of up to 10 kPa at strain levels above 15%. In contrast, the experimental pressure measurements using the Kikuhime and PPS sensors varied within 0.13 to 2.59 kPa. Youn’s CP model provided a closer fit to the experimental data, with deviations limited to within 1.9 kPa. This finding highlights the limitations of CLO3D for precision-required applications and underscores the need for more advanced, customized algorithms in virtual fit technology to ensure reliable compression garment design, particularly in medical contexts, where precise pressure control is critical for patient outcomes.