Abstract: The goal of the current study was to compare the clinical effectiveness of oral propranolol with that of oral prednisone in the treatment of infantile hemangiomas (IH). Patients treated for IH with oral propranolol were retrospectively matched with patients treated with oral prednisone according to type, location, and size of the IH and age at start of treatment. Response to treatment was evaluated by rating serial medical photographs taken 1, 2, and 6 months after initiation of treatment. Degree of clinical improvement in overall appearance (including color and size) was rated as follows: worse or stable (0), slight (<25%), moderate (25–50%), good (50–75%), or excellent (>75%). A second assessment was done using a 100-mm visual analog scale to rate improvement at 6 months. Pre and post-treatment imaging was available for several patients. Twelve pairs of infants with IH were analyzed. At 1 month, clinical improvement in the propranolol group was moderate to good in all patients. In the prednisone group, only one patient had moderate improvement, with others showing slight (7/12) or no improvement or stabilization (3/12) from baseline and one case worsening. At 6 months, the propranolol group showed good to excellent response in all cases, whereas nine in the prednisone group showed slight to moderate response. Doppler ultrasound and magnetic resonance imaging correlated with the clinical improvement in the cases in which it was performed. No major side effects were observed in either group. Propranolol appears superior to oral prednisone in inducing more-rapid and greater clinical improvement in this study. A larger prospective study comparing these two treatment modalities is warranted.