This study evaluated the longitudinal performance of a modified Lyon schuss (LS) knee examination in the detection of radiographic joint space narrowing (JSN) in knees with osteoarthritis (OA). The modified LS exam entails two to four iterative acquisitions with empirically adjusted angulation of the X-ray beam to achieve superimposition of the anterior and posterior margins of the medial tibial plateau (MTP), a marker of parallel radioanatomic alignment that the original LS exam achieves with fluoroscopically guided beam angulation. Seventy-four obese women with symptomatic knee OA underwent LS and fixed-flexion (FF, caudal 10 degrees beam angulation) X-ray exams at baseline and 1 year later. For 47 subjects, beam angulation for both LS exams was guided by fluoroscopy. For 27 subjects, the modified LS exam was performed at one or both times. Modified and original LS procedures were evaluated relative to concurrent FF radiographs with respect to the inter-margin distance (IMD) at the MTP midpoint (quality and reproducibility of alignment) and sensitivity to JSN. Compared to FF radiographs, modified LS radiographs afforded a smaller mean IMD at baseline (0.89 vs 2.06 mm, P=0.002), more reproducible IMD (mean change=0.49 vs 0.91 mm, P=0.007) and more rapid JSN (mean=0.25 vs 0.02 mm/yr, P=0.005). These differences paralleled those observed between original LS and FF procedures with respect to baseline alignment (0.96 vs 1.94 mm, P<0.001), reproducibility of alignment (0.49 vs 1.00 mm, P<0.001) and sensitivity to JSN (0.16 vs -0.01 mm/yr, P=0.007). In clinical centers where the absence of fluoroscopy equipment precludes use of the original LS protocol, a modified procedure employing iterative, empirical adjustment of the beam angle to achieve parallel radioanatomic alignment with the MTP affords a degree of superiority over the FF protocol with respect to quality and reproducibility of positioning and sensitivity to JSN in OA knees similar to that of the original.