© 2017 The Author(s). Background: Herein we describe the history, design, and rationale of the new Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and present the characteristics of patients with juvenile idiopathic arthritis (JIA) enrolled in the first 12months of operation. Methods: The CARRA Registry began prospectively collecting data in the United States and Canada in July 2015 to evaluate the safety of therapeutic agents in persons with childhood-onset rheumatic disease, initially restricted to JIA. Secondary objectives include the evaluation of disease outcomes and their associations with medication use and other factors. Data are collected every 6months and include clinical assessments, detailed medication use, patient-reported outcomes, and safety events. Follow-up is planned for at least 10years for each participant and is facilitated by a telephone call center. Results: As of July 2016, 1192 patients with JIA were enrolled in the CARRA Registry at 49 clinical sites. At enrollment, their median age was 12.4years old and median disease duration was 2.6years. Owing to preferential enrollment, patients with systemic JIA (13%) and with a polyarticular course (75%) were over-represented compared to patients in typical clinical practice. Approximately 49% were currently using biologic agents and ever use of oral glucocorticoids was common (47%). The CARRA Registry provides safety surveillance data to pharmaceutical companies to satisfy their regulatory requirements, and several independently-funded sub-studies that use the Registry infrastructure are underway. Conclusion: The new CARRA Registry successfully enrolled nearly 1200 participants with JIA in the first 12months of its operation. Sustainable funding has been secured from multiple sources. The CARRA Registry may serve as a model for the study of other uncommon diseases.