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NCI’s Patient-Derived Models Repository (NCI PDMR; pdmr.cancer.gov) has developed a variety of patient-derived models across most solid tumor histologies. These models are early passage, genetically characterized and associated with limited patient treatment history. As part of this effort, the NCI PDMR worked with the University of Nebraska Medical Center Rapid Autopsy Program and Johns Hopkins University Legacy Gift Rapid Autopsy Program to develop and optimize methods for collection, processing, and shipping of autopsy tumor material to maintain viability during overnight transit for use in patient-derived model development. These methods have been successfully transferred to two other participating rapid autopsy programs. To date, 412 autopsy tumor samples from 76 consented patients have been received for model development; 348 shipped overnight in media for next day implantation into NSG host mice and 64 cryopreserved prior to shipping for a comparative assessment of take-rate versus fresh tumor samples. On average 3-8 tumor samples, primary and metastatic, were collected post-mortem from the truncal region of each patient. Histologies include Pancreatic adenocarcinoma (n=43), Cholangiocarcinoma (n=6), Prostate adenocarcinoma (n=6), and 21 others with 1-2 patients/histology. The overall age range of enrolled patients was 5-88yo. The post-mortem cold ischemic time for collections ranged from 1.5 to 20 hours with a median of 3h (avg. 3.75h; outlier >11h removed). Collection methods were optimized to reduce contamination and increase viability of tumor tissues for successful PDX model generation. Of 348 fresh tumor samples collected to date, 69 PDX models from 33 patients have been generated (range 1-6 models/patient) and an additional 55 samples are being monitored for growth in passage 0. The largest public single-patient PDX model sets are for melanoma (899932-113-R, n=6) and two pancreatic adenocarcinomas (521955-158-R, n=6, 217524-143-R, n=4). Important methods for reducing contaminants in autopsy tumor material include sterilization of the surface of the body prior to opening, use of sterile fields, using separate sterile instruments for each collection site, rinsing the surface of the resected tumor tissue, and use of antibiotics in the collection media. The now established SOPs are publicly available on the NCI PDMR website (pdmr.cancer.gov/sops). We recommend incorporating as many of these methods as possible within the limitations of your individual site. Of the 69 models developed to date, 48 are publicly available from the NCI PDMR while the rest are undergoing quality control process prior to public release. Models developed from autopsy material provide a research tool to investigate tumor evolution, differences between primary and metastatic lesions, and assessment of differences in therapeutic response based on differences in the tumor biology. Citation Format: Yvonne A. Evrard, Michelle Eugeni, Michelle Ahalt-Gottholm, Carrie Bonomi, Suzanne Borgel, Thomas C. Caffrey, John Carter, Ting-Chia Chang, Li Chen, Kevin Cooper, Biswajit Das, Emily Delaney, Kelly Dougherty, Eleonora Duregon, Stephanie Ecker, Joe Geraghty, Marion Gibson, Lauren Hicks, Jenna Hull, Sharon Int Veldt, Shahanawaz Jiwani, Chris A. Karlovich, Jade Loewenstein, Candace Mallow, Chelsea McGlynn, Justine Mills, Tiffanie Miner, Jowaly Schneider, Tia Shearer, Savanna Styers, Shannon Uzelac, Paul Grandgenett, Michael Hollingsworth, Jody E. Hooper, P. Mickey Williams, Melinda Hollingshead, James H. Doroshow. Method development for generation of PDX models from rapid autopsy samples for the NCI patient-derived models repository [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3120.