Objective: A cluster schedule of subcutaneous allergen immunotherapy (SCIT) comprises the administration of several doses of an allergenic extract on the same day during the build-up phase in weekly intervals to achieve the maintenance dose.The objective was to determine whether the cluster SCIT schedules starting the administration with the highest available concentration vial (vial B) provided an adequate safety profile. Methods:A real-world observational study was designed. Patients between 5-65 years old with a diagnosis of rhinitis and/or bronchial asthma due to hypersensitivity to house dust mites, treated with SCIT, in cluster schedules starting with vial B (10,000 Therapeutic Units/ml), were included.Results: A total of 258 patients with a mean age of 20.3 years (95% CI 18.8-21.9), 134 females (51.9%), were included from 11 allergy units in Spanish hospitals. Eight cluster SCIT schedules were analyzed adding up 1193 doses. Forty-six patients (17.8%) suffered 89 adverse reactions (7.5% of doses): 79 local (6.6% of doses) and 10 systemic (0.8% of doses). The systemic reactions observed in seven patients were grade 1 (6) and grade 2 (4). Three patients (1.2%) withdrew the immunotherapy due to adverse reactions: systemic reaction grade 1, systemic reaction grade 2 and one local reaction. No significant safety differences between cluster schedules were observed.Conclusions: Cluster schedules of SCIT at high doses were well tolerated and reduced the build-up phase to 1-3 weeks, instead of the conventional eight weeks, thereby contributing to the improvement of patient comfort and treatment compliance.