A high-dose, accelerated escalation schedule during subcutaneous allergen-specific immunotherapy (AIT) is safe and well-tolerated in adults. However, there are no data in children and adolescents. The aim of the present trial was to assess safety and tolerability of an accelerated dose escalation schedule of an AIT with a grass pollen allergoid in children and adolescents with moderate to severe seasonal rhinoconjunctivitis in a multicenter, open-label, randomized phase II trial. The dose escalation scheme for patients in the One Strength Group included 3 injections with 1 strength B (10,000 TU/mL), whereas the dose escalation scheme for the Standard group included 7 injections with 2 strengths A (1,000 TU/mL) and B (10,000 TU/mL) of an allergoid grass pollen preparation. Overall, <i>n</i> = 50 children (<i>n</i> = 25 in each group; mean age 8.9 + 1.54 years) and <i>n</i> = 37 adolescents (<i>n</i> = 20 and <i>n</i> = 17; 14.2 + 1.62 years) were randomized. For all patients, the mean treatment duration was 59.4 days in the One Strength group and 88.6 days in the Standard group. Treatment-emergent adverse events (TEAEs) related to AIT were reported in 52 and 40% in children and 35 and 35.3% in adolescents, respectively. Systemic allergic reactions occurred in about 5% of our patients and were reported in more patients of the One Strength group (6.7 vs. 2.4%). All systemic reactions were classified as WAO Grade 1. Accelerated high-dose escalation with an aluminum hydroxide-adsorbed grass pollen allergoid can be initiated with a safety and tolerability profile comparable to the standard dose escalation schedule in children and adolescents with allergic rhinitis with or without asthma.