The physiologic benefits of high-flow nasal cannula (HFNC) therapy are well documented in the intensive care literature, yet only a handful of case reports describe its perioperative use. Our single center experience explored comprehensive applications of HFNC in the perioperative setting. Over a ten-month period, HFNC was used in the care of 85 medically complex patients either as an adjuvant or main oxygen therapy during induction of general anesthesia, maintenance of deep intraoperative sedation, and during early postoperative care. Here, we illustrate clinical scenarios in which HFNC therapy made patient care safer and describe a framework for integrating this technology into the anesthesia practice at our institution.