Postoperative radiological assessment is used to evaluate the success of knee replacement procedures. Load-bearing long-standing anterior-posterior (AP) x-rays are typically used for this assessment. For knee replacement procedures the five landmarks that are identified are: 1) hip centre; 2) femoral knee centre; 3) tibial knee centre; 4) medial malleolus; and 5) lateral malleolus. These landmarks are used to identify the femoral and tibial reference mechanical axes. However, variations in the x-ray acquisition process and foot rotation can lead to errors in this assessment. In the past, researchers have studied the effect of foot rotation and flexion on estimation of knee alignment. In our study, the use of digitally reconstructed radiographs (DRRs) allows us to vary the x-ray acquisition parameters and observe the effect of these changes to estimations of the mechanical axes. We also measured the inter-user variability in these measurements. Our results show that AP x-rays can be used to accurately estimate the femoral and tibial mechanical axes.