Whole-person care is a new paradigm for serious illness, but few programs have been robustly studied. We sought to test the effect of LifeCourse (LC), a person-centered program for patients living with serious illness, on health-care utilization, care experience, and quality of life, employing a quasi-experimental design with a Usual Care (UC) comparison group. The study was conducted 2012 to 2017 at an upper-Midwest not-for-profit health-care system with outcomes measured every 3 months until the end of life. Enrolled patients (N = 903) were estimated to be within 3 years of end of life and diagnosed with 1+ serious illness. Exclusion criteria included hospice enrollment at time of screening or active dying. Community health workers (CHWs) delivered standardized monthly 1-hour home visits based on palliative care guidelines and motivational interviewing to promote patients' physical, psychosocial, and financial well-being. Primary outcomes included health-care utilization and patient- and caregiver-experience and quality of life. Patients were elderly (LC 74, UC 78 years) and primarily non-Hispanic, white, living at home with cardiovascular disease as the primary diagnosis (LC 69%, UC 57%). A higher proportion of LC patients completed advance directives (N = 173, 38%) than UC patients (N = 66, 15%; P < .001). LifeCourse patients who died spent more days in hospice (88 +/- 191 days) compared to UC patients (44 +/- 71 days; P = .018). LifeCourse patients reported greater improvements than UC in communication as part of the care experience ( P = .016). Implementation of person-centered programs delivered by CHWs is feasible; inexpensive upstream expansion of palliative care models can yield benefits for patients and caregivers. Trial Registration: Trial NCT01746446 was registered on November 27, 2012 at ClinicalTrials.gov .