OBJECTIVE To evaluate adherence to an institutional continuous infusion propofol policy for sedation in mechanically ventilated patients, investigate the rate of propofol-related infusion syndrome (PRIS), and explore areas of improvement to enhance policy compliance and safety. METHODS This was a single center, retrospective chart review of patients admitted to a pediatric or cardiac intensive care unit within a large free-standing quaternary care pediatric hospital who received continuous propofol for non-procedural continuous sedation for at least 6 hours between 2014 and 2019. Propofol exposure (dose and duration), laboratory data, and hemodynamic outcomes of patients were evaluated. RESULTS A total of 104 patients (108 admissions and 133 treatment courses) met inclusion criteria. Policy adherence to propofol dosing and duration limitations were 70% (93/133 courses) and 68% (91/133 courses), respectively. Adherence to all elements of laboratory and hemodynamic monitoring was 23%. Hypotension and bradycardia were common among patients during propofol treatment courses. Except for hypertriglyceridemia, no significant difference in specific laboratory values were detected between patients exposed to greater than 66 mcg/kg/min (4 mg/kg/hr), compared with those exposed to less than 66 mcg/kg/min of propofol. Patients receiving therapy for longer than 48 hours had the highest rates of laboratory values associated with PRIS. No patient in the study cohort met full criteria for PRIS. CONCLUSIONS Adherence to elements of an institutional propofol policy was variable. Improvements in policy adherence may be enhanced by updating policy features, leveraging the electronic medical record order-set, and gaining consensus among key stakeholders.