The quantification of muscle weakness is useful to evaluate the health status and performance of patients and athletes. In this paper, we proposed a novel methodology to investigate and to quantify the effects induced by inaccuracy sources occurring when using a hand-held dynamometer (HHD) for knee strength measurements. The validation methodology is based on the comparison between the output of a one-component commercial HHD and the outputs of a six-component load cell, comparable in dimension and mass. An optoelectronic system was used to measure HHD positioning angles and displacements. The setup allowed to investigate the effects induced by: 1) the operator's ability to place and to hold still the HHD and 2) ignoring the transversal components of the force exchanged. The main finding was that the use of a single component HHD induced an overall inaccuracy of 5% in the strength measurements if the angular misplacements are kept within the values found in this paper (≤15°) and with a knee range of motion ≤22°. Extension trials were the most critical due to the higher force exerted, i.e., 249.4 ± 27.3 versus 146.4 ± 23.9 N of knee flexion. The most relevant source of inaccuracy was identified in the angular displacement on the horizontal plane.Index Terms-Hand-held dynamometer (HHD), knee strength, load cell, lower limb, quality assurance, strength measurements.