Postoperative nausea and vomiting (PONV) remains a ubiquitous concern for surgical outpatients with published rates ranging from 14% to 80%. An evidence-based approach was used to reduce PONV in a high-risk adult outpatient oncology population. The Observe, Orient, Decide, and Act (OODA) Loop, a rapid cycle management strategy, was adapted for use in an outpatient surgery center with six ORs. A PONV prophylaxis protocol was developed and adapted until a stable PONV rate was achieved. A combination of dexamethasone, promethazine, and ondansetron was used in patients with one to three PONV risk factors. Patients with four major risk factors received an additional intervention. The PONV rate for the final protocol stabilized below 4% by 46 weeks and remained stable through 79 weeks. The OODA paradigm provides an effective technique for interfacing health care research with clinical practice. In this case, an effective PONV prophylaxis plan was developed from within a collaborative nursing and medical setting.