Introduction: Allergic rhinoconjunctivitis and asthma are the most common IgE-mediated diseases worldwide. Allergen-specific immunotherapy (AIT) is currently the only modifying treatment for these IgE-mediated diseases, in both children and adults. Subcutaneous immunotherapy is widely used, but in patients over 65 years old there may be an increased risk of adverse reactions and a worse response to treatment. Oral immunotherapy (OIT) has been proved to be effective and safe, but currently, in most countries, it has been licensed only for patients up to 65 years old based on its technical datasheet. No studies into the efficacy and safety of this type of immunotherapy in patients older than 65 years old have been published. Case Presentation: We present four patients older than 65 years old with a diagnosis of moderate seasonal rhinoconjunctivitis and moderate-persistent seasonal pollen-induced asthma. Off-label use of oral immunotherapy (OIT) for grass pollen was prescribed, due to the severity of their rhinoconjunctivitis symptoms and worsening of asthma symptoms during the spring. Improvement in the rhinoconjunctivitis and asthma symptoms was reported by all patients since the first spring season and was maintained during the following two years of follow-up. There were no systemic reactions and only two patients initially had self-limiting oral pruritus Conclusion: Oral immunotherapy for pollens appears to be a convenient, effective, and safe option in older patients (>65 years) with comorbidities after a three-year treatment. This is, to the best of our knowledge, the first report of the off-label use of OIT in patients over 65 years old with symptoms of allergic rhinoconjunctivitis and asthma.