The efferent control chain for an upper-limb myoelectric prosthesis can be separated into 3 key areas: signal generation, signal acquisition, and device response. Data were collected from twenty trans-radial myoelectric prosthesis users using their own clinically prescribed devices, to establish the relative impact of these potential control factors on user performance (user functionality and everyday prosthesis usage). By identifying the key factor(s), we can guide future developments to ensure clinical impact. Skill in generating muscle signals was assessed via reaction times and signal tracking. To assess the predictability of signal acquisition, we inspected reaction time spread and undesired hand activations. As a measure of device response, we recorded the electromechanical delay between electrode stimulation and the onset of hand movement. Results suggest abstract measures of skill in controlling muscle signals are poorly correlated with performance. Undesired activations of the hand or incorrect responses were correlated with almost all kinematics and gaze measures suggesting unpredictability is a key factor. Significant correlations were also found between several measures of performance and the electromechanical delay; however, unexpectedly, longer electromechanical delays correlated with better performance. Future research should focus on exploring causes of unpredictability, their relative impacts on performance and interventions to address this.