This study investigated the effectiveness of high-fidelity immersive simulation education to support inter-professional hospital clinical staff in recognizing and responding to aggression, violence, and clinical deterioration of patients admitted with mental health issues. Increased incidents of aggression and violence have been reported in many clinical hospital settings, especially in mental health wards. Patients experiencing severe psychological distress/ agitation can result in the escalation of physiological symptoms such as chest pain, difficulty breathing, traumatic injury, etc. Mental health staff do receive aggression prevention training and medical emergency team training. However, there is added complexity when dealing with a mental health patient who is exhibiting aggressive, violent behaviour while also experiencing a medical or psychological emergency. Therefore, mental health staff needed a combined training programme that enhanced their delivery of recovery focussed care, de-escalation, and medical emergency crisis resource management skills. This study used a prospective quasi experimental research design with repeated measures. Hospital clinical staff were immersed in two mental health emergency response and clinical deterioration scenarios and debriefing sessions. Self-efficacy was evaluated using a 10-item validated tool which addressed non-technical skills of Leadership, Management, Communication, and Teamwork. The sample consisted of 122 clinical staff, with the majority from mental health wards (52%; n = 63) who were nurses (68%; n = 83). Mean self-efficacy scores increased significantly across the three time points (F = 11.555; df = 2; P = 0.000). Post hoc pairwise comparisons showed that self-efficacy scores increased between pretest (mean 62.9; n = 122) and posttest 1 (mean 83.2; n = 122) and follow up, 3 months later (posttest 2; mean 81.9; n = 24). Between pre-and posttest 1, significant improvements in self-efficacy were observed for both the Leadership/Management domain (t = 8.2; df 119; P < 0.000; 95% CI 13.3-21.7) and the Communication/Teamwork domain (t = 8.0; df 119; P < 0.000; 95% CI 11.1-18.4). Immersive simulation with high fidelity education was found to be effective in improving hospital nursing and medical staffs' confidence, when responding to incidents of aggression/violence and clinical deterioration of a mental health patient.