The international ColoCare Study aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic markers) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with short-term and long-term patient-reported and clinical outcomes among patients with colorectal cancer. ColoCare is recruiting newly diagnosed patients with colorectal cancer across six sites in the United States and one site in Heidelberg, Germany. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. The combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource and research infrastructure to study multiple promising biologic and epidemiologic characteristics with cutting-edge approaches that predict outcomes among patients with colorectal cancer. The ColoCare Study brings together a transdisciplinary team of clinicians, epidemiologists, and laboratory scientists to address novel questions of colorectal cancer prognosis.