Usability problems associated with electronic health records can adversely impact clinical workflow, leading to inefficiencies, error, and even clinician burnout. The work presented in this dissertation is concerned with understanding and improving clinical workflow. Towards that end, it is necessary to model physical and cognitive aspects of task performance in clinical settings. Task completion can be significantly impacted by the navigational efficiency of the electronic health record (EHR) interface. Workflow modeling of the EHR-mediated workflow could help identify, diagnose and eliminate problems to reduce navigational complexity. The research goal is to introduce and validate a new biomedical informatics methodological workflow analysis framework that combines expert-based and user-based techniques to guide effective EHR design and reduce navigational complexity. These techniques are combined into a modified walkthrough that aligns user goals and subgoals with estimated task completion time and characterization of cognitive demands. A two-phased validation of the framework is utilized. The first is applied to single EHR-mediated workflow tasks, medication reconciliation (MedRec), and medication administration records (MAR) to refine individual aspects of the framework. The second phase applied the framework to a pre/post EHR implementation comparative analysis of multiple workflows tasks. This validation provides evidence of the framework's applicability and feasibility across several sites, systems, and settings. Analysis of the steps executed within the interfaces involved to complete the medication administration and medication reconciliation and patient order management tasks have provided a basis for characterizing the complexities in EHR navigation. An implication of the work presented here is that small tractable changes in interface design may substantially improve EHR navigation, overall usability, and workflow. The navigational complexity framework enables scrutinizing the impact of different EHR interfaces on task performance and usability barriers across different sites, systems, and settings.