Widespread use of gait or motion analysis in the diagnosis of patients with locomotor pathology and the subsequent planning and assessment of treatment has been limited because of its reliability, particularly in evaluating frontal and transverse plane components. This is because spatial reconstruction of the musculoskeletal system and calculation of its kinematics and kinetics via a skin marker-based multi-link model are subject to marker skin movement artefacts. Traditional methods treat each body segment separately without imposing joint constraints, resulting in apparent dislocations at joints predominantly because of skin movement artefacts. An optimisation method for the determination of the positions and orientations of multi-link musculoskeletal models from marker co-ordinates is presented. It is based on the minimisation of the weighted sum of squared distances between measured and model-determined marker positions. The model imposes joint constraints. Numerical experiments were performed to show that the new method is capable of eliminating joint dislocations and giving more accurate model position and orientation estimations. It is suggested that, with joint constraints and a global error compensation scheme, the effects of measurement errors on the reconstruction of the musculoskeletal system and subsequent mechanical analyses can be reduced globally. The proposed method minimises errors in axial rotation and ab/adduction at the joints and may extend the applicability of gait analysis to clinical problems.