Purpose: This qualitative study aimed to explore and interpret the meaning and essence of end-of-life care as experienced by nurses in internal medicine wards caring for patients who had completed advance directives (AD). It sought to understand the psychological conflicts, ethical dilemmas, and evolving perceptions of care encountered by nurses during the end-of-life process. Additionally, the study focuses on providing foundational data to support the clinical implementation of the AD system, thereby contributing strategies that improve the quality of end-of-life care and uphold patients' rights and dignity in hospital settings. Methods: A qualitative content analysis was conducted using in-depth, semi-structured interviews with 12 nurses from internal medicine wards in tertiary hospitals located in Seoul and surrounding metropolitan areas. Participants had direct experience in providing end-of-life care for patients with ADs. Interviews focused on capturing nurses’ real-life experiences and reflections related to such care. Data were analyzed systematically following the eight-step qualitative content analysis method proposed by Downe and Wamboldt, allowing for the identification of meaningful categories, themes, and patterns. Results: Analysis revealed five major themes and 16 subthemes. The major themes included: (1) Experiences of repeated end-of-life care and advance directives in internal medicine wards, reflecting the frequent encounters of nurses with terminally-ill patients and their ADs; (2) Multifaceted experiences of end-of-life care based on ADs, suggesting the complexities of care shaped by the presence or absence of ADs; (3) Limitations and dilemmas in AD implementation, highlighting the ethical conflicts arising from low public awareness and inconsistent clinical practices; (4) Shifts in perceptions of life and death, including the development of practical attitudes towards death through repeated exposure to dying patients, illustrating the evolving views of nurses; and (5) Hopes for improving end-of-life care in internal medicine wards, emphasizing the need for enhanced care environments, educational support, and institutional backing. Conclusion: The findings underscore the importance of increasing awareness and improving the clinical application of ADs. Establishing systematic support structures is essential to respect patient autonomy and enhance the quality of end-of-life care in internal medicine wards.