OBJECTIVES: Clinical efficacy and cost-effectiveness of immunotherapy in allergic disease caused by various allergens is demonstrated by several published studies, but economic value is still far from being appreciated by local decision makers. Scope of this work was to provide the Regional decision makers with real world information on the use and impact of immunotherapy in terms of efficacy on symptoms, use and cost of drugs in patients affected by rhinoconjunctivitis (RC) with or without asthma (A), caused by ragweed seasonal allergy. METHODS: Observational study, of precoseasonal sublingual (SLIT) or preseasonal subcutaneous immunotherapy (SCIT) versus non-immunotherapy (NSIT). Patients enrolled by a network of specialist centres from Lombardia, were randomly assigned to one of the study groups and were allowed to take any additional medication needed to control RC and A symptoms; effectiveness was measured as global symptom score rated by the patient on a VAS at last visit; drug consumption was measured as days of medication recorded by the patient on a weekly diary card during the peak season; drug cost was calculated by applying Italian NHS prices. RESULTS: For the first year of immunotherapy, 163 adults were analyzed (SLIT N=67 M=48%, age 39+/-9.1; SLIT N=34 M=62%, age 41+/-8.1; NSIT N=62 M=53%, age 36+/-9.2); 25% of SLIT patients were affected by A as compared to 47% of SCIT and 37% of NSIT patients; 55% of SLIT patients were treated with high dose SLIT. The mean number of drug treatment days/patient was lower for SLIT patients 26.15+/-30.1 vs. NSIT 58.7+/-43.4 (p<0.0001) and for SCIT patients 33.0+/-45.7 vs NSIT 58.7+/-43.4 (p<0.05); similarly the mean total cost/patient of drug treatment was lower with SLIT €28.19 vs SCIT €33.9 and NSIT €59.2. CONCLUSION: SLIT and SCIT can effectively reduce use and cost of drug treatment in adults affected by rhinoconjunctivitis with/without asthma caused by ragweed in Lombardia.