IntroductionFailure to rescue is defined as mortality after complications during hospital care. Incidence ranges 10.9%–13.3% and several national reports such as National Confidential Enquiry into Patient Outcomes and Death and National Institute of Clinical Excellence CG 50 highlight failure to rescue as a significant problem for safe patient care.To avoid failure to rescue events, there must be successful escalation of care. Studies indicate that human factors such as situational awareness, team working, communication and a culture promoting safety contribute to avoidance of failure to rescue events. Understanding human factors is essential to developing work systems that mitigate barriers and facilitate prompt escalation of care. This qualitative evidence synthesis will identify and synthesise what is known about the human factors that affect escalation of care.Methods and analysisWe will search MEDLINE (Ovid), EMBASE (Ovid) and CINAHL, between database inception and 2018, for studies describing human factors affecting failure to rescue and/or care escalation. A search strategy was developed by two researchers and a medical librarian. Only studies exploring in-hospital (ward) populations using qualitative data collection methods will be included. Screening will be conducted by two researchers. We are likely to undertake a thematic synthesis, using the Thomas and Harden framework. Selected studies will be assessed for quality, rigour and limitations. Two researchers will extract and thematically synthesise codes using a piloted data extraction tool to develop analytical themes.Ethics and disseminationThe qualitative evidence synthesis will use available published literature and no ethical approval is required. This synthesis will be limited by the quality of studies, rigour and reproducibility of study findings. Results will be published in a peer-reviewed journal, publicised at conferences and on social media.PROSPERO registration numberCRD42018104745.