Purpose: The purpose of this study was to evaluate the usability of a prototype personal digital assistant (PDA)-based decision support system for the management of obesity through usability testing with end-users (Advanced Practice Nurses [APNs]) prior to its implementation in clinical settings. Methods: This descriptive study used observational and think aloud techniques to address the research question: what usability problems are perceived by end-users? Five APNs were provided with the scenarios and the list of tasks to evaluate the application. Their verbalizations were recorded through Morae usabil ity software. Data analysis was based on the data captured through Morae, transcriptions, notes, and the end-user survey. Results: End-users completed all the required tasks without encountering a severe usability problem, and agreed that the system was easy to use. clear, concise, and useful. Usability issues that were unrecognized by the developer or usability experts were identified by APNs. The usability problems were categorized according to positive characteristics, negative characteristics, and recommendations. The usability issues were discussed with the project team members, and solutions were suggested to improve the user interface of the PDA-based decision support system before the final implementation. Conclusions: This approach had an important impact on making the system easier to use and more useful from the perspective of design and content. The results of this evaluation provided iterative feedback regarding the design and implementation of the PDA-based decision support system for the management of obesity.