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Background: The purpose of this study was to investigate the size differences of 19 different femoral component placements from the standard position in total knee arthroplasty using 3-dimensional virtual surgery. Methods: Three-dimensional bone models were reconstructed from the computed tomography data of 101 varus osteoarthritic knees. The distal femoral bone was cut perpendicular to the femoral mechanical axis (MA) in the coronal plane. Twenty different component placements consisting of 5 cutting directions (perpendicular to MA, 3° and 5° extension relative to MA [3°E-MA and 5°E-MA, respectively], and 3° and 5° flexion relative to MA [3°F-MA and 5°F-MA, respectively]) in the sagittal plane, 2 rotational alignments (clinical epicondylar axis [CEA] and surgical epicondylar axis [SEA]), and 2 rotational types of anterior reference guide (central [CR] and medial [MR]) were simulated. Results: The mean anteroposterior dimension of femur ranged from 54.3 mm (5°F-MA, SEA, CR) to 62.5 mm (5°E-MA, CEA, MR). The largest and smallest differences of anteroposterior dimension from the standard position (3°F-MA, SEA, and CR) were 7.1 ± 1.3 mm (5°E-MA, CEA, and MR) and −1.2 ± 0.2 mm (5°F-MA, SEA, and CR), respectively. Multiple regression analysis revealed that flexion cutting direction, SEA, and CR were associated with smaller component size. Conclusions: The femoral component size can be affected easily by not only cutting direction but also the reference guide type and the target alignment. Our findings could provide surgeons with clinically useful information to fine-tune for unintended loose or tight joint gaps by adjusting the component size.