Mechanical performance of clavicle fracture fixation plates is often evaluated using finite element (FE) analysis. Typically, these studies use simplified loading conditions and assume a transversal fracture orientation. However, the loading conditions and fracture orientation influence how the fracture site and thus fixation plate is loaded. In this study, a musculoskeletal model that included the clavicle muscles and scapulohumeral rhythm was defined based on previously published models. The standard OpenSim workflow (inverse kinematics, inverse dynamics, static optimization, and joint reaction analysis) was used to calculate muscle and joint contact forces based on 3D marker data collected in three subjects during seven activities of daily living (ADL). These loading conditions were then applied to a 3D clavicle model with three different fracture orientations and the mean resulting moments on both fragments were calculated to assess fracture stability. Magnitude of glenohumeral contact forces showed good agreement with instrumented shoulder prosthesis data, whereas simulated muscle activations were comparable to experimental EMG data. An oblique fracture orienting from superomedial to inferolateral was the least self-stabilizing. The loading to which the clavicle is exposed during ADL tasks is more complex than the simplified loading conditions typically used as boundary conditions in FE analyses of clavicle fracture fixation plates. Additionally, transversal fractures did not represent the least self-stabilizing fracture orientation, and thus calculated stresses in the plate could be underestimated. Therefore, more complex loading conditions and evaluation of a midshaft fracture running from superomedial to inferolateral is more relevant in FE analyses of midshaft clavicle fracture fixation plates.