Background: The healthcare sector is responsible for 7% of greenhouse gas (GHG) emissions in the Netherlands. However, this is not well understood on an organizational level. This research aimed to assess the carbon footprint of the Erasmus University Medical Center to identify the driving activities and sources. Methods: A hybrid approach was used, combining a life cycle impact assessment and expenditure-based method, to quantify the hospital’s carbon footprint for 2021, according to scope 1 (direct emissions), 2 (indirect emissions from purchased energy), and 3 (rest of indirect emissions) of the GHG Protocol. Results were disaggregated by categories of purchased goods and services, medicines, specific product groups, and hospital departments. Results: The hospital emitted 209.5 kilotons of CO2-equivalent, with scope 3 (72.1%) as largest contributor, followed by scope 2 (23.1%) and scope 1 (4.8%). Scope 1 was primarily determined by stationary combustion and scope 2 by purchased electricity. Scope 3 was driven by purchased goods and services, of which medicines accounted for 41.6%. Other important categories were medical products, lab materials, prostheses and implants, and construction investment. Primary contributing departments were Pediatrics, Real Estate, Neurology, Hematology, and Information & Technology. Conclusion: This is the first hybrid analysis of the environmental impact of an academic hospital across all its activities and departments. It became evident that the footprint is mainly determined by the upstream effects in external supply chains. This research underlines the importance of carbon footprinting on an organizational level, to guide future sustainability strategies.