Objective To evaluate changes in infantile hemangioma tissue before and after propranolol therapy, using gray-scale and color Doppler ultrasound imaging. Study Design Case series with chart review. Setting Tertiary pediatric hospital. Subjects and Methods Medical records and image studies of head and neck infantile hemangioma patients treated with propranolol, identified in a quality improvement database, were reviewed. Patients with imaging before and at least 4 weeks following the initiation of treatment were included. Data collected included sex, age, location, and concurrent treatment. Student t tests were used to evaluate change in cutaneous lesion area, volume, and vessel density. Logistic regression was used to compare lesion area, volume, and vessel density. Results Of the 177 patients identified, 19 met inclusion criteria. Fourteen of 19 were female, and 5 of 19 were older than 1 year. Mean lesion area change with treatment was 13.0 cm2 (range, −2.8 to 28.9 cm2, P = .05). Measured volume change was a mean of 10.3 cm3 (range, 1.5-19.2 cm3, P = .01). Mean vessel density change was 4.4 vessels per cm2 (range, 2.5-6.3 vessels per cm2, P < .01). Treatment decreased clinically determined hemangioma area proportionately less than gray-scale and color Doppler ultrasound measured lesion volume. Gray-scale and color Doppler ultrasound measured treatment response did not differ with sex, lesion location, or age at propranolol initiation. Conclusion Gray-scale and color Doppler ultrasound imaging of propranolol-treated infantile hemangiomas detected a significant reduction in lesion volume and vessel density. Patient age at propranolol treatment and concomitant corticosteroid use did not affect lesion volume change.