Knee joint laxity or instability is a common problem that may have detrimental consequences for patients. Unfortunately, assessment of knee joint laxity is limited by current methodologies resulting in suboptimal diagnostics and treatment. This paper presents a novel method for accurately measuring non-invasive knee joint laxity in four degrees-of-freedom (DOF). An arthrometer, combining a parallel manipulator and a six-axis force/moment sensor, average mean difference for translations of 0.08 mm and an average limit of agreement between-1.64 mm and 1.80 mm. The average mean difference for rotations was 0.10°and the limit of agreement were between-0.85° and 1.05°. The presented method eliminates several limitations present in current methods and may prove a valuable tool for assessing knee joint laxity. Current stress radiography is also only assessing single plane laxity, but is not limited by low reliability (Schulz et al., 2005) or STA (Garavaglia et al., 2007). The radiation exposure from such measurements may, however, induce serious health risks for both the patient and operator making the method unsuitable for many applications (Balonov and Shrimpton, 2012). Joint instability must be assessed in multiple DOF in order to fully understand the complexity of the joint structures and the interplay between ligaments (Hirschmann and Müller, 2015). Neither clinical tests, arthrometry nor 1D stress radiography possesses the potential to obtain this information. Furthermore, these methods potentially over-constrain the joint during measurements, by restricting out-of-plane motion, making it appear more stable and potentially shift the load distribution unnaturally in the joint (Woo et al., 1999). Methods capable of measuring unconstrained knee joint laxity in multiple DOF not restricted by the above limitations are a prerequisite to progress the field of research in knee instability and advance current clinical assessment of joint instability. Novel methods utilizing robotics for assessing knee joint laxity has, therefore, recently emerged (Branch et al., 2015; Lorenz et al., 2015). These methods exercise high repeatability and accuracy in the application of forces, however, they are still limited by their inability to measure true bone motion due to STA. By combining robotic technology with new medical image modalities, the aforementioned limitation can be overcome which may make it possible to conceive a laxity measurement method with high accuracy, multiplanar assessment and unaffected by STA. Therefore, this paper proposes such a novel method for measuring knee joint laxity in multiple DOF, combining parallel manipulator technology and low dose biplanar x-ray acquisition. Methods Development An in vivo arthrometer was custom developed, combining a parallel manipulator (H-820, Physik Instrumente, Germany) and a six axis force/moment (F/M) sensor (Omega85 SI-1900-80, ATI Industrial Automation, USA) (see Fig. 1). The parallel manipulator has a manufacturer reported repeatability of ±1 µm and the F/M sensor has a re...