Background: Medical student exposure to stressors is associated with depression, burnout, somatic distress, decreases in empathy, serious thoughts about dropping out of medical school, suicidal ideation, and poor academic performance. Despite this, there have been no recent, multicenter, qualitative studies assessing medical studentsā perceptions of their greatest stressor(s). Objective: The goal of this study was to identify the most significant stressors noted by medical students themselves, in order to inform the development of programs and policies to reduce medical student distress. Design: Medical students from the nine schools in the state of Florida were invited to complete an anonymous online questionnaire assessing wellness and distress. Students were notified that all responses were voluntary and that individual responses would not be linked to themselves or their program. This paper focuses on studentsā responses to fixed-response items regarding their experience of stress and open-ended responses to the following question: āWhat do you consider to be the greatest stressor(s) facing medical students?ā Qualitative data were analyzed using the Grounded Theory method of data analysis. Results: Results confirmed the impact of several stressors highlighted in previous studies (e.g., excessive workload, difficulties with studying and time management, conflicts in workālife balance and relationships, medical school peer relations, health concerns, and financial stressors). However, students also reported unique system-level concerns that have not consistently been highlighted in past research (e.g., medical school administrative failures, concerns about lack of assistance with career planning, and assessment-related performance pressure. Conclusions: Though individually focused interventions have demonstrated some success, medical students self-report stressors that may be better addressed through system-level changes.