Introduction: Patients who are homeless and/or using substances rely heavily on emergency departments (ED) for medical care, and present with complex medical and social needs. Negative physician attitudes towards this population undermine the therapeutic relationship, compromising the quality of medical care provided. The objective of this study was to determine the attitudes of emergency physicians towards homeless and substance-using patients. Methods: Using a Modified Total Design approach, we conducted a cross-sectional survey of emergency physicians at five different healthcare locations in Calgary, Alberta, Canada. Attitudes were assessed using two validated measures, the Health Care Providers Attitudes Towards the Homeless Inventory (HPATHI), and the Short Understanding of Substance Use Scale (SUSS). Surveys were self-administered by respondents between March and December 2013. Results: A total of 117 physicians completed the survey (response rate 48%). 28% of respondents resented the amount of time it takes to see homeless patients, and 32% believed caring for homeless patients was not financially viable; 57% felt overwhelmed by the complexity of problems that homeless people have. Physicians with extra training in addiction medicine or health care for the homeless had more positive attitudes than physicians with no extra training; physician attitudes worsened over time towards both populations. Conclusion: Physicians feel overwhelmed when caring for patients who are homeless and/or substance using and negative attitudes worsened over time. Extra training in addiction medicine or healthcare for the homeless is associated with more positive attitudes. Possible strategies to improve attitudes should include a multifaceted approach addressing individual physician knowledge deficits, as well as expanded access to resources in the ED and community, designed to deal with the complex needs of these populations.