Infantile hemangioma (IH) is the most common benign tumor occurring during childhood. We hypothesized that, in addition to already known risk factors, such as female sex, prematurity, and low birthweight (LBW), antenatal vaginal bleeding and progesterone therapy would be highly associated with IH. We randomly selected 650 individuals with IH and matched them with 650 children of the same age and nationality without IH. Trained investigators used a standardized questionnaire to collect data from both groups, including demographic, prenatal, and perinatal characteristics. Prematurity (p < .001, odds ratio [OR] = 2.22, 95% confidence interval [CI] = 1.44–3.41), LBW (p < .001, OR = 3.10, 95% CI = 1.87–5.16) and female sex (p < .001, OR = 2.06, 95% CI = 1.65–2.58) were significantly associated with IH. Maternal vaginal bleeding during the first trimester was shown to be an independent risk factor according to logistic regression analyses (p < .001, OR = 1.6, 95% CI = 1.36–1.91), which was most evident in those receiving progesterone therapy to prevent miscarriage (p < .001, OR = 2.11, 95% CI = 1.77–2.51). Subgroup analyses revealed that the effect was more pronounced in female than in male infants (OR = 2.82, 95% CI = 2.39–3.34). In addition to the known relationships, the present study identified a close relationship between maternal vaginal bleeding and progesterone therapy during early pregnancy and IH. Twins appeared to have a higher incidence of IH than singletons.