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Purpose: Usability evaluations can improve the usability and workflow integration of clinical decision support (CDS).Traditional usability testing using scripted scenarios with thinkaloud protocol analysis provide a useful but incomplete assessment of how new CDS tools interact with users and clinical workflow.“Near-live” clinical simulations are a newer usability evaluation tool that more closely mimics clinical workflow and that allows for a complementary evaluation of CDS usability as well as impact on workflow.Methods: This study employed two phases of testing a new CDS tool that embedded clinical prediction rules (an evidence-based medicine tool) into primary care workflow within a commercial electronic health record.Phase I applied usability testing involving “think-aloud” protocol analysis of 8 primary care providers encountering several scripted clinical scenarios.Phase II used “near-live” clinical simulations of 8 providers interacting with video clips of standardized trained patient actors enacting the clinical scenario.In both phases,all sessions were audiotaped and had screen-capture software activated for onscreen recordings.Transcripts were coded using qualitative analysis methods.Results: In Phase I,the impact of the CDS on navigation and workflow were associated with the largest volume of negative comments (accounting for over 90% of user raised issues) while the overall usability and the content of the CDS were associated with the most positive comments.However,usability had a positive-to-negative comment ratio of only 0.93 reflecting mixed perceptions about the usability of the CDS.In Phase II,the duration of encounters with simulated patients was approximately 12 min with 71% of the clinical prediction rules being activated after half of the visit had already elapsed.Upon activation,providers accepted the CDS tool pathway 82% of times offered and completed all of its elements in 53% of all simulation cases.Only 12.2% of encounter time was spent using the CDS tool.Two predominant clinical workflows,accounting for 75% of all cases simulations,were identified that characterized the sequence of provider interactions with the CDS.These workflows demonstrated a significant variation in temporal sequence of potential activation of the CDS.Conclusions: This study successfully combined “think-aloud” protocol analysis with “nearlive” clinical simulations in a usability evaluation of a new primary care CDS tool.Each phase of the study provided complementary observations on problems with the new onscreen tool and was used to refine both its usability and workflow integration.Synergistic use of “thinkaloud” protocol analysis and “near-live” clinical simulations provide a robust assessment of how CDS tools would interact in live clinical environments and allows for enhanced early redesign to augment clinician utilization.The findings suggest the importance of using complementary testing methods before releasing CDS for live use.