Abstract Background As providers look to scale high-acuity care in the patient home setting, hospital-at-home is becoming more prevalent. The traditional model of hospital-at-home usually relies on care delivery by in-home providers, caring for patients in urban communities through academic medical centers. Our objective is to describe the process and outcomes of Mayo Clinic’s Advanced Care at Home (ACH) program, a hybrid virtual and in-person hospital-at-home model combining a single, virtual provider-staffed command center with a vendor-mediated in-person medical supply chain to simultaneously deliver care to patients living near an urban hospital-at-home command center and patients living in a rural region in a different US state and time zone. Methods A descriptive, retrospective medical records review of all patients admitted to ACH between July 6, 2020, and December 31, 2021. Patients were admitted to ACH from an urban academic medical center in Florida and a rural community hospital in Wisconsin. We collected patient volumes, age, sex, race, ethnicity, insurance type, primary hospital diagnosis, 30-day mortality rate, in-program mortality, 30-day readmission rate, rate of return to hospital during acute phase, All Patient Refined-Diagnosis Related Groups (APR-DRG) Severity of Illness (SOI), and length of stay (LOS) in both the inpatient-equivalent acute phase and post-acute equivalent restorative phase. Results Six hundred and eighty-six patients were admitted to the ACH program, 408 in Florida and 278 in Wisconsin. The most common diagnosis seen were infectious pneumonia (27.0%), septicemia / bacteremia (11.5%), congestive heart failure exacerbation (11.5%), and skin and soft tissue infections (6.3%). Median LOS in the acute phase was 3 days (IQR 2–5) and median stay in the restorative phase was 22 days (IQR 11–26). In-program mortality rate was 0% and 30-day mortality was 0.6%. The mean APR-DRG SOI was 2.9 (SD 0.79) and the 30-day readmission rate was 9.7%. Conclusions The ACH hospital-at-home model was able to provide both high-acuity inpatient-level care and post-acute care to patients in their homes through a single command center to patients in urban and rural settings in two different geographical locations with favorable outcomes of low mortality and hospital readmissions.