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Background: For some stroke patients and caregivers, navigating the transition between hospital discharge and returning home is associated with substantial psychosocial and health-related challenges. Currently, no evidence-based standard of care exists that addresses the concerns of stroke patients and caregivers during the transition period. Objectives of the Michigan Stroke Transitions Trial (MISTT) are to test the impact of a social worker home-based case management program, as well as an online information and support resource, on patient and caregiver outcomes after returning home., Methods: The Michigan Stroke Transitions Trial is a randomized, pragmatic, open (un-blinded), 3-group parallel designed superiority trial conducted in 3 Michigan hospitals. Eligible participants are adult acute stroke patients discharged home directly or within 4 weeks of being discharged to a rehabilitation facility. The patient's primary caregiver is also invited to participate. Patients are randomized on the day they return home using a randomized block design. Consented patients discharged to a rehabilitation facility who do not go home within 4 weeks are dropped from the study. The 2 study interventions begin within a week of returning home and conclude 3 months later. The 3-group design compares usual care to either a home-based social worker stroke case management (SWSCM) program, or a combination of the SWSCM program plus access to an online information and support resource (MISTT website). Outcomes data are collected at 7-days and 90-days by trained telephone interviewers. Primary patient outcomes include the PROMIS global 10 score (a generic Quality of Life scale), and the Patient Activation Measure (PAM). Caregiver outcomes include the Bakas Caregiving Outcomes Scale. Final analysis will be based on 214 randomized acute stroke patients. To accommodate subjects excluded due to prolonged rehabilitation stays, as well as those lost-to-follow-up, up to 315 patients will be consented., Discussion: The MISTT study will determine if a home-based case management program designed around the needs and preferences of stroke patients and caregivers, alone or in combination with a patient-centered online information and support resource can improve stroke survivor and caregiver outcomes 3 months after returning home., Trial Registration: ClinicalTrials.gov: NCT02653170 (Protocol ID: 135457). Registered April 9, 2015.