Background: Active patient participation is a patient safety priority for health care. Yet, patients and their preferences are less understood. The aim of the study was to explore hospitalised patients’ preferences on participation in their care and safety activities in Sweden. Methods: Exploratory qualitative study. Data were collected over a four-month period in 2013 and 2014. Semi-structured interviews were conducted with 20 patients who were admitted to one of four medical wards at a university hospital in Sweden. Data were analysed using thematic analysis. Results: Nine men and eleven women, whose median age was 72 years (range 22–89), were included in the study. Five themes emerged with the thematic analysis: endorsing participation; understanding enables participation; enacting patient safety by participation; impediments to participation; and the significance of participation. This study demonstrated that patients wanted to be active participants in their care and safety activities by having a voice and being a part of the decision-making process, sharing information and possessing knowledge about their conditions. These factors were all enablers for patient participation. However, a number of barriers hampered participation, such as power imbalances, lack of patient acuity and patient uncertainty. Patients’ participation in care and patient safety activities seemed to determine whether patients were feeling safe or ignored. Conclusion: This study contributes to the existing literature with fundamental evidence of patients’ willingness to participate in care and safety activities. Promoting patient participation begins by understanding the patients’ unique preferences and needs for care, establishing a good relationship and paying attention to each patient’s ability to participate despite their illness.