Background: Both sublingual and subcutaneous immunotherapies have a documented clinical efficacy, but only a few comparative studies have been performed. Objectives: To evaluate and compare the long-term efficacies of subcutaneous and sublingual immunotherapy. Methods: One hundred and ninety-three patients with house dust mite allergies, out of an original total of 230, were treated with subcutaneous and sublingual house dust mite-specific immunotherapies for 3 years and also observed for 3 years after discontinuation of the treatment. The patients were randomized into 2 groups: the sublingual group (97 patients) and the subcutaneous group (96 patients). The therapy’s success was evaluated using the symptom score, skin prick test results, and the nasal allergen challenge score. The patients were evaluated at the beginning of the study, at the end of years 1, 2, and 3, and also at the end of the 1st and 3rd years after discontinuation of the specific immunotherapy treatment. Results: Immunotherapy induced a significant improvement during the treatment and the follow-up period. We found a greater improvement in the subcutaneous group compared to the sublingual group when we looked at the comparative results of the total 6 years. Conclusion: We suggest subcutaneous immunotherapy for patients with perennial allergic rhinitis due to the better results that were obtained during our study period. Nevertheless, sublingual immunotherapy is now accepted by WHO as a valid alternative to the subcutaneous route and should be used in all patients who require immunotherapy and do not accept the subcutaneous route of allergen administration.

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