In recent years, oral propranolol has risen from serendipitous discovery to first-line, albeit off-label, therapy for infantile hemangiomas (IHs). This retrospective study explored the utility of a 24-hour hospitalization for the initiation of propranolol therapy in children with problematic IHs by evaluating the effects of systemic propranolol on hemodynamics and blood sugar levels. Thirty-one children were admitted to the hospital to begin oral propranolol at a dose of 2 mg/kg/per day. Heart rate (HR), blood pressure (BP), and blood glucose (BG) measurements were obtained at baseline and 1 to 3 hours before and after each dose of propranolol. No caregivers reported any adverse effects during the hospitalization. On average, HR decreased by 5 beats per minute (bpm) (p < 0.01) and systolic BP decreased by 4 mmHg (p < 0.01) after propranolol administration. There was no statistically significant change in diastolic BP or BG with propranolol therapy. Over the first three doses of propranolol we saw statistically significant attenuation of the effects of propranolol on HR, with HR approaching baseline values during the hospitalization (p = 0.04). We did not see statistically significant changes in BP over the course of three doses of propranolol. This study suggests that 24-hour hospitalization with hemodynamic monitoring may not be necessary for safe initiation of propranolol therapy in otherwise healthy infants. Parental education on frequent feedings to decrease the chance of hypoglycemia may be as effective as 24-hour hospitalization.