Medication safety is increasingly challenging patient safety in growing aging populations. Developing positive patient safety cultures is acknowledged as a primary goal to improve patient safety, but evidence on the interventions to do so is inconclusive. Nursing home residents are often cognitively and physically impaired and are therefore highly reliant on frontline health care providers. Thus, interventions to improve medication safety of nursing home residents through patient safety culture among providers are needed. Using cocreative partnerships, integrating knowledge of residents and their relatives, and ensuring managerial support could be beneficial. The primary aim of the Safe Medication of Nursing Home Residents Through Development and Evaluation of an Intervention (SAME) study is to improve medication safety for nursing home residents through developing an intervention by gaining experiential knowledge of patient safety culture in cocreative partnerships, integrating knowledge of residents and their relatives, and ensuring managerial support. The fully integrated mixed method study will be conducted using an integrated knowledge translation approach. Patient safety culture within nursing homes will first be explored through qualitative focus groups (stage 1) including nursing home residents, their relatives, and frontline health care providers. This will inform the development of an intervention in a multidisciplinary panel (stage 2) including cocreators representing the medication management process across the health care system. Evaluation of the intervention will be done in a randomized controlled trial set at nursing homes (stage 3). The primary outcome will be changes in the mean scale score of an adapted version of the Danish "Safety Attitudes Questionnaire" (SAQ-DK) for use in nursing homes. Patient safety-related outcomes will be collected through Danish health registers to assess safety issues and effects, including medication, contacts to health care, diagnoses, and mortality. Finally, a mixed methods analysis on patient safety culture in nursing homes will be done (stage 4), integrating qualitative data (stage 1) and quantitative data (stage 3) to comprehensively understand patient safety culture as a key to medication safety. The SAME study is ongoing. Focus groups were carried out from April 2021 to September 2021 and the workshop in September 2021. Baseline SAQ-DK data were collected in January 2022 with expected follow-up in January 2023. Final data analysis is expected in spring 2024. The SAME study will help not only to generate evidence on interventions to improve medication safety of nursing home residents through patient safety culture but also to give insight into possible impacts of using cocreativity to guide the development. Thus, findings will address multiple gaps in evidence to guide future patient safety improvement efforts within primary care settings of political and scientific scope. ClinicalTrials.gov NCT04990986; https://clinicaltrials.gov/ct2/show/NCT04990986. DERR1-10.2196/43538.