This is the full dataset of the 2021 Cryo-EM Map-based Model Ligand Challenge sponsored by EMDataResource (www.emdataresource.org, challenges.emdataresource.org, model-compare.emdataresource.org). The Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein/nucleic-acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: (1) E. coli beta-galactosidase with inhibitor, (2) SARS-CoV-2 RNA-dependent RNA polymerase with covalently bound nucleotide analog, and (3) SARS-CoV-2 ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. File Descriptions: 2021-EMDataResource-Ligand-Challenge-web.pdf: Archive of challenges website content describing the challenge including News, Overview, Goals, Model Evaluation, Timeline, Targets, How to Participate, Q&A, Advisory Committee, Ligand Images T010X.zip: Submitted model files for each target (mmCIF and PDB formats) used for analyses S1_Ligand_Challenge_Statistics_Submission_Form.pdf: Overall model statistics, model submission form guide S2_submission_metadata.xlsx: Complete set of metadata collected for each submitted model S3_ligandchallengescores.xlsx: Compiled set of scores for this challenge from the model-compare site. WrapUp_MeetingAgendaLigandChallenge.pdf: Agenda of the July 26-28 2021 wrap up meeting zoom_discussion_mc_results.mp4: July 14 Model-Compare site analysis live demo recording