Currently, propranolol is the most preferred systemic therapy for problematic infantile hemangiomas (IHs). However, the side effects such as bronchial hyperreactivity may be intolerable. The aim of this study was to evaluate the frequency, risk factors and management of intolerable side effects (ISEs) during propranolol therapy. In total, 1260 children were studied. The incidence of ISEs was 2.1% (26 patients). Severe sleep disturbance was the most common reason for propranolol cessation, accounting for 65.4% of cases. In total, 23 and 3 patients received atenolol and prednisolone as second-line therapy, respectively. Treatment response was observed in 92.3% (24/26) of cases (showing excellent or good response to therapy). No toxicity-related permanent treatment discontinuation occurred during atenolol or prednisolone therapy. In the univariate analysis, younger age, premature birth, and lower body weight were associated with ISEs (P < 0.05). In the multivariate analysis, only age (95% confidence interval [CI]: 1.201–2.793, P = 0.009) and body weight (95% CI: 1.036–1.972, P = 0.014) were associated with ISEs. Our study suggests that ISEs are rare in patients with IHs who are treated with propranolol. Predictive factors for ISEs include younger age and lower body weight. Atenolol and prednisolone are effective and safe alternatives to propranolol in the treatment of refractory IHs.