For health services, improving organizational health literacy responsiveness is a promising approach to enhance health and counter health inequity. A number of frameworks and tools are available to help organizations boost their health literacy responsiveness. These include the Ophelia (OPtimising HEalth LIteracy and Access) approach centered on local needs assessments, co-design methodologies, and pragmatic intervention testing. Within a municipal cardiac rehabilitation (CR) setting, the Heart Skills Study aimed to: (1) Develop and test an organizational health literacy intervention using an extended version of the Ophelia approach, and (2) evaluate the organizational impact of the application of the Ophelia approach. We found the approach successful in producing feasible organizational quality improvement interventions that responded to local health literacy needs such as enhanced social support and individualized care. Furthermore, applying the Ophelia approach had a substantial organizational impact. The co-design process in the unit helped develop and integrate a new and holistic understanding of CR user needs and vulnerabilities based on health literacy. It also generated motivation and ownership among CR users, staff, and leaders, paving the way for sustainable future implementation. The findings can be used to inform the development and evaluation of sustainable co-designed health literacy initiatives in other settings.