Hospital-acquired venous thromboembolism (VTE) is a common and preventable adverse event with hospitalized patients described as being at 100 times greater risk than people in the community. The purpose of this study was to compare the ease-of-use and required cognitive effort during the use of two chemoprophylaxis assessment and assignment protocols to identify the protocol with the highest usability and effectiveness. The two compared protocols consisted of the current risk stratification (protocol R) and a proposed intent-to-treat method (protocol 1). The purpose of the intent-to-treat protocol was to use clinical pathway methodology to reduce the amount of cognitive effort utilized by resident physicians during the treatment of VTE. Forty-one medicine residents participated in an online comparison of the two different protocols (R and 1) for treating VTE prophylaxis using six unique patient scenarios. Statistical analyses found that protocol 1 (52.8 sec.) produced significantly faster mean scenario completion times than protocol R (79.6 sec.) along with significantly (33%) more correct chemoprophylaxis assignment outcomes over all six scenarios and scenario difficulty levels (easy, medium or hard). The results of this study indicate that protocol 1 enhances performance by reducing cognitive errors, completion time and unnecessary protocol steps by using the proposed clinical pathway methodology.