Abstract Patient portals potentially serve as a platform for patients to easily access their health information and more easily communicate with their provider, if designed and developed appropriately for the user. When patients use portals it also affords the opportunity to have their health information preserved over time. Despite these benefits, the majority of the US population does not ever access or engage with patient portals. With the Office of the National Coordinator for Health Information Technology now mandating open application programming interfaces (APIs), which will allow for the development of patient portals that can receive data from any EHR vendor product, the effective design of portals for all users is now even more critical. Many patient portals suffer from poor usability and do not provide patients with the information they need in an intuitive format. Further, patient needs vary by demographics and health status. The objective of the proposed research is to identify and characterize the factors differentiating patient portal users from non-users within five population subgroups, and to develop clear design guidelines to represent their needs. We will conduct a large cross-sectional survey of diverse patient portal users and non-users, by sampling from novel crowd-sourcing platforms (for broad reach) and patients within a large diverse health system. We will apply identified user preferences to develop personas. We follow with a usability analysis of common patient portal products to determine whether these products meet the identified user needs. The outputs will include user- centered guidelines for patients across the spectrum of usage and portal engagement. This has the potential to improve patient portals based on a deep understanding of patient needs, identification of the shortcomings of current patient portals, and learnings from those systems with successful adoption (incentivized or otherwise). This project utilizes the extensive expertise of the research team in human factors and safety science, health IT, and health equity research. Contributions from this research will include a fundamental understanding of what information patients seek when accessing their patient portal and current challenges with existing patient portals. The findings from our research will be disseminated through traditional academic outlets, but also directly to providers and associations who ultimately customize vendor products according to their patients’ needs.