During scanning, sonographers often assume significant awkward postures which may lead to musculoskeletal pain and disability. Two exoskeletons were tested as an ergonomic intervention by sonographers during transthoracic echocardiograms (TTE). Four sonographers each performed TTEs using right- and left-handed scanning techniques, with and without two different passive upper extremity exoskeletons in two two-by-two experimental designs. Posture, muscle activity, and subjective discomfort scores were recorded. Of the two exoskeletons tested, the updated FLEX® design significantly reduced 10th percentile upper trapezius muscle activity during left hand scanning, while the AIRFRAME® did not impact muscle activity across all the muscles of interest. Furthermore, there was a slight decrease in the self-reported discomfort levels in their wrist and hands associated with performing TTE when wearing Exos1 compared to baseline. However, participants experienced issues with comfort, limitations on their range of motion (ROM), and interference with tasks with both exoskeletons. Collectively, the results indicate that the tested exoskeleton designs provide minimal benefit for reducing upper extremity muscle workload during TTE ultrasonography tasks. •Upper extremity pain is predominant in cardiac sonographers.•Two commercially available exoskeletons provided minimal benefit for shoulder muscles of cardiac sonographers performing TTEs.•Upper extremity exoskeletons for cardiac sonography applications need to be designed with shallow abduction engagement angles.