Background: Forty-six percent of individuals with mental health conditions have long-term physical illness, while 30% of individuals with long-term physical conditions have a mental illness. Physical and psychiatric comorbidities are of significant concern to medical, psychiatry, and primary care services, with policy, strategy, and literature highlighting the need to better address this interface. Simulation training has been proposed as a tool to improve clinicians' management of physical and psychiatric comorbidities. This study is the first to evaluate interprofessional simulation in improving management of such comorbidity. Method: Participants (n = 63) were doctors and nurses from emergency, medical, psychiatric, and community services across primary and secondary care in South London. Quantitative and qualitative measures were completed before and after a one-day interprofessional simulation course addressing clinical care for physical and psychiatric comorbidities. Results: Knowledge, confidence, and attitudes scores showed statistically significant improvements post-course with large effect sizes. Thematic analyses highlighted the development of interprofessional working, clinical skills, reflective practice, leadership and teamwork, and communication skills. Conclusion: Simulation training has the potential to improve professional development and clinical practice, with participants reporting increased abilities to provide better care to patients with physical and psychiatric comorbidities, exemplifying the case for increased simulation training in health care education. (C) 2016 International Nursing Association for Clinical Simulation and Learning. Published by Elsevier Inc. All rights reserved.