Objectives: (1) To investigate the healthcare experiences of individuals with mental health and/or substance use disorders (SUDs) who seek medical care in the emergency department (ED) for physical health concerns (e.g., abdominal pain), and (2) to explore recommendations for improving these patients' care experiences. Although this population suffers from a high disease burden and disproportionately seeks care in the ED, surprisingly little research has examined their experiences. Study Setting and Design: Qualitative study employing grounded theory and semi-structured interviews with patients with mental health and/or SUD(s) (identified via health records) seeking care for a physical health concern during an ED visit to an academic medical center in the Northeastern USA. Longer follow-up interviews were conducted via telephone. Interviews occurred between February 2018 and January 2019. Data Sources and Analytical Sample: We transcribed and coded digital recordings of interviews with 50 patients at two time periods. We used constant comparative analysis throughout interviewing, coding, and analysis. Principal Findings: Most participants were White (80%), non-Hispanic (84%), and female (72%). Three key themes emerged, revealing a broad range of negative and positive patient care experiences that are influenced by provider, treatment, and healthcare system factors. Findings demonstrate that stigma and perceived biases due to mental health and/or SUDs extend to medical care experiences not directly related to these conditions (e.g., dismissive, rushed, unprofessional care, medical errors). Participants also identified positive care experiences (e.g., attentive, communicative, efficient, quality care), which informed recommendations for improving care. Conclusions: Understanding care experiences of vulnerable patient populations is critically important for informing interventions to improve their healthcare quality and safety. Findings underscore the need for additional education and training for providers, integrated behavioral healthcare, and widespread changes to the healthcare system. Localized interventions that target stigma and mismatches between patients' care expectations and ED capabilities are also needed.