Background: Electronic health records (EHRs) are an elementary part of the work of registered nurses (RNs) in healthcare. RNs are the largest group of healthcare workers, and their experiences with EHRs and their informatics competence play a crucial role in a fluent workflow. The present study examined EHR usability factors and nurses' informatics competence factors related to self-reported time pressure and psychological distress. Methods: A nationwide survey was conducted for working-age registered nurses in 2017. The study sample included 3607 nurses (5% men) in Finland. The association of age, sex, employment sector, EHR usability factors, and nurses' informatics competence factors with time pressure and psychological distress were examined with analyses of covariance. Results: The EHR usability factors that were associated with high time pressure were low EHR reliability and poor user-friendliness. Regarding the nurses' informatics competence factors, only low e-Care competence was associated with time pressure. Of the EHR usability factors, low EHR reliability and low support for cooperation were associated with high psychological distress. Of the nurses' informatics competence factors, low e-Care competence was associated with high psychological distress. Conclusions: Unreliability and poor user-friendliness of EHRs seem to be prominent sources of time pressure and psychological distress among registered nurses. User-friendly EHR systems and digital tools in healthcare are needed. Nurses' competence to use eHealth tools to tailor patient care should be strengthened through organizational and regional actions. For example, house rules about how to use eHealth tools and instructions on common practices in cooperation with other organizations could be useful.