Limited health literacy is a common but often unrecognized problem associated with poor health outcomes. Well-validated screening tools are available to identify and provide the opportunity to intervene for at-risk patients in a resource-efficient manner. This is a multimethod study describing the implementation of a hospital-wide routine health literacy assessment at an academic medical center initiated by nurses in April 2014 and applied to all adult inpatients. Results were documented in the electronic health record, which then generated care plans and alerts for patients who screened positive. A nursing survey showed good ease of use and adequate patient acceptance of the screening process. Six months after hospital-wide implementation, retrospective chart abstraction of 1,455 patients showed that 84% were screened. We conclude that a routine health literacy assessment can be feasibly and successfully implemented into the nursing workflow and electronic health record of a major academic medical center.