Conventional subcutaneous immunotherapy (SCIT) for allergy treatment needs several injections over several weeks to reach the maintenance dose. Shorter up-dosing regimens are desired but limited by the potential of side effects. This study was designed to compare the safety of Depigoid (Laboratorios LETI, Spain)-SCIT 1 day versus 3 weeks up-dosing in patients with Type 1 allergy caused by clinically relevant sensitization against tree pollen, grass pollen, and house-dust mites. A total of 303 patients with confirmed allergic rhinitis/conjunctivitis were included. A rush build-up schedule administering 0.2 mL and then 0.3 mL of the concentrate at day 1 followed by 0.5 mL at day 28 was compared with a conventional 4-week build-up schedule. The number of patients reaching the maintenance phase without systemic reactions or major deviation from treatment schedule were compared. Of the rush 91.8% and in the conventional group 90.9% reached the maintenance phase without dose modification. Neither the proportions of patients with systemic reactions (5.8% rush versus 2% conventional) nor the proportions of patients with local reactions differed significantly between the two regimens (24% rush versus 11% conventional). There was no difference with respect to the applied allergen group. The proposed rush build-up schedule for the immunotherapy treatment with depigmented allergoids without premedication is safe and not inferior to the conventional schedule.