Background: There is a recognized need to increase participation in ALS clinical research among people living with ALS (PALS). One of the potential barriers to participation among PALS living in metropolitan areas is a perceived or real lack of collaboration across ALS research centers. The Minneapolis-St Paul metropolitan area has a unique opportunity to overcome this barrier, as ALS providers in four academic centers share University of Minnesota faculty appointments and participate actively in regular regional clinical and research meetings hosted by the ALS Association Minnesota/North Dakota/ South Dakota chapter. Recognizing an opportunity to combine complementary strengths across centers, the ALS providers at the ALS Association Certified Treatment Centers of Excellence at Hennepin County Medical Center and the University of Minnesota have joined forces with the HealthPartners Neuroscience Center and the Minneapolis Veterans Affairs Medical Center to form the Twin Cities ALS Research Consortium (TCALSRC). All clinical research at TCALSRC centers endeavor to include principal- and co-investigators from at least two participating centers and, to whatever extent possible using courtesy appointments, investigators are encouraged to recruit and evaluate their own patients to all TCALSRC studies at whichever institution is contracted as the study site. Monthly meetings assure that all investigators and coordinators are up-to-date on current and planned projects and have an opportunity to share ideas. Methods and results: The TCALSRC model encourages active investigator and PALS engagement throughout the metropolitan region, regardless of the study site, thus enhancing recruitment as well as value of the site to sponsors and consortia. Contracting sites are rotated among participating centers with a view toward equal participation, but also based upon the complementary research interests of individual principal investigators and the unique resources that might be available at certain institutions. Discussions: The TCALSRC is currently exploring regional expansion to engage other outstanding ALS clinicians in Minnesota and the Dakotas. The TCALSRC is a model for advancing ALS local and regional clinical research, with several centers committed to advancing ALS research and care.