BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinicalffects. OBJECTIVE: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. METHODS: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. RESULTS: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were euro3800, an amount that was largely misspent. CONCLUSION: Real-life persistence is better in SCIT users than in SLIT users, although itis low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.