Background: An estimated 30-50% of patients admitted to acute medical care settings experience co-morbid physical and mental illness. Research suggests that health professionals in these settings find managing this patient group challenging. A number of studies have investigated health professional's attitudes and perceptions however there is limited research that investigates the lived experience in a current Australian healthcare context. The aim of this study was to explicate an in-depth description of the health professional's experience when caring for patients experiencing co-morbid physical and mental illness in Australian acute medical care settings. Methods: A phenomenological design was undertaken with six participants representing nursing and medical disciplines. In 2013-2014 one-on-one semi-structured interviews were used and the data collected underwent thematic analysis using an extended version of Colaizzi's phenomenological inquiry. Results: Six themes emerged including - challenging behaviours, environmental and organisational factors, lack of skills, knowledge and experience, hyper-vigilance and anxiety, duty of care and negative attitudes with an overarching theme of fear of the unknown. Conclusions: Staff in acute medical care settings were unsure of patients with mental illness and described them as unpredictable, identifying that they lacked requisite mental health literacy. Regular training is advocated.