Approximately 80 million inpatient and outpatient surgeries are performed annually in the United States. Widely variable and fragmented perioperative care exposes these surgical patients to lapses in expected standard of care, increases the chance for operational mistakes and accidents, results in unnecessary and potentially detrimental care, needlessly drives up costs, and adversely affects the patient healthcare experience. The American Society of Anesthesiologists and other stakeholders have proposed a more comprehensive model of perioperative care, the Perioperative Surgical Home (PSH), to improve current care of surgical patients and to meet the future demands of increased volume, quality standards, and patient-centered care. To justify implementation of this new healthcare delivery model to surgical colleagues, administrators, and patients and maintain the integrity of evidenced-based practice, the nascent PSH model must be rigorously evaluated. This special article proposes comparative effectiveness research aims or objectives and an optimal study design for the novel PSH model.