Summary Stanford University and the SLAC National Accelerator Laboratory (SLAC) propose to host a National Center for Cryoelectron Microscopy – The Stanford-SLAC CryoEM Center (S2C2) – to meet the emerging national need for cryoEM as a tool for atomic-resolution structural biology. The proposed S2C2 will (1) establish, and keep at the forefront, state-of-the-art cryo-electron microscopes to satisfy users’ needs for atomic-resolution image data, (2) archive image data with appropriate metadata, (3) provide computing resources to assess data quality in real time, (4) inform and recruit potential users across the U.S. about the public accessibility of the Center, (5) establish an open, fair, transparent and efficient process to select user proposals based on scientific impact and specimen readiness, regardless of users’ geographic locations or affiliations, (6) help users to overcome technical hurdles and enable them to obtain high-resolution cryoEM structures quickly with a rigorous validation protocol, (7) form and facilitate a user network to exchange information seamlessly, (8) train users to become independent cryoEM investigators, (9) integrate user and trainee feedback into a continuous loop of facility enhancement, and (10) optimize operations to achieve the above tasks effectively and efficiently. Dr. Wah Chiu, the Contact PI, has decades of experience developing high-resolution cryoEM technologies and directing research and training enterprises across multiple institutions. Drs. Michael Schmid, Georgios Skiniotis , and Britt Hedman, also PIs of the Center, bring complementary expertise in cryoEM, structural biology, and management and operation of large-scale national user facilities. A Center Director of Operations, three skilled cryoEM specialists, a technical assistant, and a user facility administrator will carry out the S2C2’s day-to-day operations, including data collection, quality assessment, and cross-training. This S2C2 will reside in a new building at SLAC. It will leverage SLAC’s expertise in serving thousands of users each year at its renowned X-ray synchrotron and free electron laser user facilities. An Advisory Committee comprised of external expert scientists as well as user representatives will provide advice regarding S2C2 operations and development. Our Center will build on the unique strengths and support from Stanford and SLAC, and will create a unique environment that combines high throughput cryoEM data generation with training the next generation of cryoEM scientists.