OBJECTIVES: Long-term compliance and persistence has been poorly assessed in allergen immunotherapy for allergic rhinitis, a frequently applied but costly (€1543/year, (2009 figures)), treatment for an increasingly prevalent disease. Allergen immunotherapy with pollen and/or mites requires a three to five year long course of treatment. Immunotherapy may be administered sublingually(SLIT) at home, or subcutaneously(SCIT) at the doctor’s office. This study aims to assess the  long-term compliance and persistence of allergen immunotherapy and the costs of premature cessation of immunotherapy. METHODS: Data from over 8,000 users who started allergen immunotherapy between 1994 and 2009 were extracted from a representative, commercially available database (the PHARMO institute, The Netherlands). Data included drug name, type of allergen, amount of drug prescribed, route of administration, type of prescribing physician, pharmacy visit date, socioeconomic status (SES), sex, age, pharmacy costs and revenues. Compliance was defined as the number of late pharmacy visits, persistence was defined as the total duration of treatment of at least three years. Time to treatment discontinuation was analyzed using Kaplan-Meijer curves and Cox proportional hazard models. RESULTS: A total of 48% of SLIT users and 37% of SCIT users discontinued therapy before the first year, and 23% of SLIT users and 37% of SCIT users continue immunotherapy for at least three years. SLIT is predominantly prescribed by GPs, and SCIT by allergologists. 2.6 late pharmacy visits were recorded per patient (SD 2.2). Sex was not a significant predictor of persistence, but higher age, SES, and a rural place of residence were. Nonpersistent behavior is associated with drug costs of over 50M euros over the observation period. CONCLUSIONS: A significant difference in persistence exists between users of SLIT and SCIT in favor of the latter. The high costs associated with non-persistence ask for both patient and doctor education and warrants the use of compliance devices.