Introduction Oral propranolol is a first-line treatment for infantile hemangiomas (IH). This study aims to describe the results of treating IH with propranolol only or initial propranolol therapy followed by laser therapy, surgical excision, corticosteroid therapy, or a second cycle of propranolol. Methods Our patient population included pediatric patients (<18 years of age) diagnosed with IH at Monroe Carell Junior Children’s Hospital at Vanderbilt University Medical Center between August 2009 to July 2017. Patient demographics, IH clinical features, and treatment data were extracted from the electronic medical record. Results Three hundred forty patients with IH were included in this study, with a prevalence of focal lesions (71%) and a total of 279 (82%) IH located on the head/neck. Lesions of the head had a statistically significant association with PHACE syndrome (p<0.001). Most patients initiated propanolol treatment before the age of 6 months (71%), with continuation for ≥6 months (69%). Upon discontinuation of propranolol, 14 (4%) patients required a second cycle of propranolol for regrowth. After controlling for IH location, patients with a family history of hemangiomas or cardiac abnormalities were 3.6 times more likely to need a second round of propranolol treatment (OR, 3.6; 95% Confidence Interval 1.14-11.19) (P=0.03). Conclusion The study confirms propranolol’s effectiveness and safety, reinforcing the need for early intervention and close monitoring following treatment termination to prevent regrowth. Ultimately, this research contributes to advancing the understanding and treatment of IH, aiming to optimize patient outcomes and reduce morbidity.