Background: In-person conference attendance contributes significantly to a professional’s annual greenhouse gas (GHG) emissions. However, estimating conference emissions has often relied on assumptions about attendee numbers and travel, especially for investigations of medical conferences. This project aims to address these limitations by utilizing actual attendance data from the American Society of Clinical Oncology’s (ASCO) Annual Meetings. The objectives of this project are to establish a quantitative baseline of conference-associated emissions for different formats (in-person, virtual, and hybrid) and simulate changes to conference parameters with evaluation of associated emissions to provide recommendations for sustainable changes. Methods: Data was provided by ASCO including the number of attendees, zip codes of origin, and attendance method (in-person versus virtual) for their 2019-2022 Annual Meetings. Using a variety of conservative assumptions, emissions were calculated with consideration of the following factors: travel versus virtual attendance, conference space utilization, hotel stays, and electricity. The results were stratified by country, attendance method, and year, and differences in emissions were assessed with t-tests. Simulations were conducted to evaluate the impact of different conference sizes, locations, and formats on emissions. Results: The highest estimated GHG emissions were associated with the in-person 2019 conference, totaling 37,251 metric tons of carbon dioxide equivalents. While international attendees accounted for the largest proportion of emissions (>50%) in all years, optimizing conference locations models only reduced emissions by 3%. However, simulations of hub-and-spoke models showed the potential for larger decreases of up to 86%, and various hybrid models offered similar emission savings. Furthermore, hybrid conferences in 2020 and 2021 demonstrated increased attendee diversity with a higher percentage of international attendees compared to the in-person 2019 conference (44% international attendance in 2019 versus 53% in 2020 and 54% in 2021). Conclusions: This study not only quantifies the emissions impact of alternative conference formats but also highlights the importance of diversity, equity, and inclusion (DEI) considerations in reducing emissions. While travel remains a significant contributor to conference emissions, conference models focusing solely on location optimization were not as effective as hybrid models in reducing emissions. Hybrid models may present an opportunity to effectively mitigate GHG emissions while maintaining networking opportunities and cultivating inclusivity for attendees from diverse backgrounds.