Transgender individuals face numerous health disparities and report negative experiences with health care providers related to their gender identity. Significant gaps in medical education regarding transgender health persist despite calls for increased sexual and gender minority content. The purpose of this student-led study was to assess the effectiveness of a half-day educational intervention on first- and second-year medical students' attitudes and knowledge of transgender health. Students and faculty members collaborated to develop an educational session on transgender health. This content was presented to first- and second-year medical students at Integrated Grand Rounds, a pedagogical method in which basic science and clinical faculty members co-present didactic content interspersed between live patient interviews and student-led small group discussions. Student participants (n = 138) completed voluntary 9-item pre- and post-session surveys assessing comfort with and knowledge of transgender medicine. Students' comfort with and perceived knowledge about transgender patients increased significantly between pre- and post-test. Students' knowledge of transgender medicine standards of care also improved, though not all items reached significance. A half-day educational intervention improved many facets of medical students' attitudes and knowledge about transgender patients. The significant disparities in physical health, mental health and access to care currently experienced by transgender persons in the United States warrants the continued testing and refinement of educational interventions for future and practising providers. Students' comfort with transgender patients increased significantly between pre- and post-test.