The goal of this study was to investigate the use of cognitive modeling to assess the usability of an upper-limb prosthesis with a focus on mental workload responses. Prior studies have investigated usability of upper-limb prostheses with subjective surveys and physiological measures. However, these approaches have limitations, including subject recall of conditions and physiological response contamination by head and body movements and user speech during task performance as well as sensitivity to physical fatigue and room lighting conditions. Cognitive modeling was used to assess mental workload in use of transradial upper-limb prosthesis. A case study was conducted with a participant with upper-limb amputation using two different types of electromyography-based control schemes, including conventional direct control (DC) and pattern recognition (PR) control in order to compare cognitive model outcomes with mental workload assessment using eye-tracking measures. Cognitive models time estimates were also compared with actual task completion time results from the case study to further assess the validity of cognitive modeling as an analytical tool for evaluating upper limb prosthesis usability. Findings of both the cognitive models and case study revealed the PR mode to be more intuitive, reduce cognitive load, and increase efficiency in prosthetic control as compared to the DC mode. Results of the present study revealed that cognitive modeling can be used as an analytical approach for assessing upper-limb prosthetic device usability in terms of workload outcomes. Future studies should validate the present findings with more precise time estimations and a larger user sample size.