Background Physical restraint is widely used in intensive care units to ensure patient safety, manage agitated patients, and prevent the removal of medical equipment connected to them. However, physical restraint use is a major healthcare challenge worldwide. Aim This study aimed to explore nurses' experiences of the challenges of physical restraint use in intensive care units. Methods This qualitative study was conducted in 2018–2019. Twenty critical care nurses were purposively recruited from the intensive care units of four hospitals in Tehran, Iran. Data were collected via in-depth semi-structured interviews, concurrently analyzed via Graneheim and Lundman's conventional content analysis approach, and managed via MAXQDA software (v. 10.0). Findings Three main themes were identified (i) organizational barriers to effective physical restraint use (lack of quality educations for nurses about physical restraint use, lack of standard guidelines for physical restraint use, lack of standard physical restraint equipment), (ii) ignoring patients' wholeness (their health and rights), and (iii) distress over physical restraint use (emotional and mental distress, moral conflict, and inability to find an appropriate alternative for physical restraint). Conclusion Critical care nurses face different organizational, ethical, and emotional challenges in using physical restraint. Healthcare managers and authorities can reduce these challenges by developing standard evidence-based guidelines, equipping hospital wards with standard equipment, implementing in-service educational programs, supervising nurses' practice, and empowering them for finding and using alternatives to physical restraint. Nurses can also reduce these challenges through careful patient assessment, using appropriate alternatives to physical restraint, and consulting with their expert colleagues.