Cluster immunotherapy is becoming an alternative to conventional IT due to its shorter schedule, but the safety of such schedule is still controversial. At present, only few studies assess the risk of immunotherapy in a prospective manner, in well-controlled patients, using the same extract and intending to evaluate a single schedule. The aim of the present study is to evaluate the safety of a cluster immunotherapy administration regimen. A total of 91 outpatients (41 male and 50 female), with a mean age of 25 years old (range: 16-50) were included. Sixty-one patients were diagnosed mild to moderate asthma and 30 rhinoconjunctivitis. Forty-six of the enrolled patients were sensitised to pollen (Lolium perenne and/or Olea europea), 38 to Dermatophagoides pteronyssinus and 7 to Alternaria alternata. Patients received specific immunotherapy following a five-week cluster schedule. It was considered as a preseasonal treatment, that is, it was accomplished before olive and grass initial pollinating months in this area (March--April). A total 1029 injections were administered during the induction phase. Adverse reactions were assessed and classified according to the EAACI criteria. The average number of visits to maximum dose was 6 (range 2-10), and 70 patients (77%) reached the maximum between 5-7 visits. In each of the visits an average of 2 (range 1-3) injections were administered. Eighty-one of the 91 initially enrolled patients (89%) completed the cluster schedule. The total number of reactions were 47 (24 local and 23 systemic). No fatal reactions were observed. Since the total number of administered injections was 1029, the relative frequency of adverse reactions was 4.6% (2.3% local and 2.2% systemic). The percentage of patients affected by systemic reaction was 18% and by local reaction 14%. No relationship can be shown between adverse reactions and gender or disease. However, a clear relationship with the composition of immunotherapy has been shown, with a lower risk of adverse reactions associated with the extract of D. pteronyssinus. The shorter period required to achieve the maintenance dose, with a similar frequency of adverse events, leads to the conclusion that the proposed administration regimen can be an alternative to conventional schedule to increase patient compliance.