Beta-blockers are a highly promising treatment modality for complicated infantile hemangiomas (IH). However, data on propranolol as first-line treatment, objective outcome measures and impact on hemodynamics in young infants is limited. We retrospectively evaluated a homogenous group of infants with proliferating complicated IH treated with propranolol (2 mg/kg/day). Outcome was assessed by blinded evaluation of clinical photographs by visual analogue scale (VAS), ultrasound examination and ophthalmological review (if appropriate). Tolerance and hemodynamic variables were recorded over time, including a 2-day in-patient observation at the initiation of therapy. Twenty-five infants (median age 3.6 (1.5–9.1) months) were included in the study. The median follow-up-time was 14 (9–20) months and 14 patients completed treatment at a median age of 14.3 (11.4–22.1) months, after a duration of 10.5 (7.5–16) months. In all patients, there was significant fading of colour (with a VAS of −9 (−6 to −9) after 7 months) and significant decrease in size of the IH (with a VAS of −8 (−3 to −10) after 7 months). Median thickness of the lesions assessed by ultrasound at baseline and after 1 month was 14 (7–28) mm and 10 (5–23) mm, respectively (p < 0.01). In children with periocular involvement, astigmatism and amblyopia resolved rapidly within 8 weeks. The overall tolerance of propranolol was good, and no relevant hemodynamic changes were noted. Conclusion: Our report supports the excellent effect and good tolerance of this novel therapy, and we propose the use of propranolol as first-line treatment for IH.