OBJECTIVE: To prospectively evaluate a cohort of patients with infantile hemangioma in the midline lumbosacral region for spinal anomalies to determine the positive predictive value of infantile hemangioma for occult spinal anomalies and to make evidence-based recommendations for screening. STUDY DESIGN: A multicenter prospective cohort study was performed at 9 Hemangioma Investigator Group sites. RESULTS: Intraspinal abnormalities were detected in 21 of 41 study participants with a lumbosacral infantile hemangioma who underwent a magnetic resonance imaging evaluation. The relative risk for all patients with lumbosacral infantile hemangiomas for spinal anomalies was 640 (95% confidence interval [CI], 404-954), and the positive predictive value of infantile hemangioma for spinal dysraphism was 51.2%. Ulceration of the hemangioma was associated with a higher risk of having spinal anomalies. The presence of additional cutaneous anomalies also was associated with a higher likelihood of finding spinal anomalies; however, 35% of the infants with isolated lumbosacral infantile hemangiomas had spinal anomalies, with a relative risk of 438 (95% CI, 188-846). The sensitivity for ultrasound scanning to detect spinal anomalies in this high-risk group was poor at 50% (95% CI, 18.7%-81.3%), with a specificity rate of 77.8% (95% CI, 40%-97.2%). CONCLUSIONS: Infants and children with midline lumbosacral infantile hemangiomas are at increased risk for spinal anomalies. Screening magnetic resonance imaging is recommended for children with these lesions.