ABSTRACT - OVERALL Total joint arthroplasty (TJA) is the most common and fastest growing surgery in the nation with more than 7 million Americans currently living with artificial joints. Despite the high surgery volume, the evidence base for TJA procedures, technologies and associated interventions are limited. Many surgical approaches, implants or surgical technologies (computer navigation, robotic surgery) are adopted based on theoretical grounds with limited clinical evidence of effectiveness and safety. The wider TJA research community needs access to large, high quality and rich data sources, state-of-the-art clinical research standards and information technologies to overcome methodological and practical challenges in studies of surgical and nonsurgical interventions in TJA. American Joint Replacement Research-Collaborative (AJRR-C) is a Core Center for Clinical Research exclusively focused on TJA. The overarching goal of AJRR-C is to facilitate innovative, methodologically rigorous and interdisciplinary clinical research that will directly improve TJA care and the outcomes. AJRR-C is a disease (TJA) and theme-focused Center providing shared methodological expertise, education, data and infrastructure resources. AJRR-C leverages big data resources for TJA research, provides customized methodology resources in epidemiology, biostatistics, health services research and medical informatics, and has established synergistic interactions around an integrated Resource Core (American Joint Replacement Registry – AJRR). The Specific Aims of AJRR-C are: (1) To provide administrative and scientific oversight of AJRR-C activities (Administrative Core), (2) To provide integrated and customized services, access to large databases and novel analytical methods for clinical research in TJA (Methodology Core); and (3) To meet the unique data and infrastructure needs of the TJA research community and to strengthen the national capacity for large-scale observational and interventional studies in TJA (Resource Core). AJRR-C is integrated within the long- standing and highly centralized clinical research environment of Mayo Clinic, thereby leveraging existing expertise and infrastructure resources. AJRR-C activities are evaluated using robust metrics to ensure continuous evaluation, flexibility and improvement in response to the most pressing needs of the TJA research community.