Visualization can be a powerful tool to comprehend data sets, especially when they can be represented via hierarchical structures. Enhanced comprehension can facilitate the development of scientific hypotheses. However, the inclusion of excessive data can make visualizations overwhelming. We developed a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS). In this study, we evaluated the usability of VIADS for visualizing data sets of patient diagnoses and procedures coded in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We used mixed methods in the study. A group of 12 clinical researchers participated in the generation of data-driven hypotheses using the same data sets and time frame (a 1-hour training session and a 2-hour study session) utilizing VIADS via the think-aloud protocol. The audio and screen activities were recorded remotely. A modified version of the System Usability Scale (SUS) survey and a brief survey with open-ended questions were administered after the study to assess the usability of VIADS and verify their intense usage experience with VIADS. The range of SUS scores was 37.5 to 87.5. The mean SUS score for VIADS was 71.88 (out of a possible 100, SD 14.62), and the median SUS was 75. The participants unanimously agreed that VIADS offers new perspectives on data sets (12/12, 100%), while 75% (8/12) agreed that VIADS facilitates understanding, presentation, and interpretation of underlying data sets. The comments on the utility of VIADS were positive and aligned well with the design objectives of VIADS. The answers to the open-ended questions in the modified SUS provided specific suggestions regarding potential improvements for VIADS, and the identified problems with usability were used to update the tool. This usability study demonstrates that VIADS is a usable tool for analyzing secondary data sets with good average usability, good SUS score, and favorable utility. Currently, VIADS accepts data sets with hierarchical codes and their corresponding frequencies. Consequently, only specific types of use cases are supported by the analytical results. Participants agreed, however, that VIADS provides new perspectives on data sets and is relatively easy to use. The VIADS functionalities most appreciated by participants were the ability to filter, summarize, compare, and visualize data. RR2-10.2196/39414.