Abstract Background There is considerable interest in improving the scoring methods for evaluating the efficacy of allergen immunotherapy (AIT) and to show if this is associated with clinically meaningful results from the patient's perspective. We aimed to assess the efficacy and clinical relevance of a 300 index of reactivity (IR) 5‐grass pollen sublingual immunotherapy (SLIT) tablet in children, adolescents and adults with moderate to severe grass‐induced allergic rhinoconjunctivitis (ARC) with or without controlled asthma using the combined symptom and medication score CSMS 0‐36 . Methods The data of the European population that participated in 3 Phase III, international, randomized double‐blind placebo‐controlled clinical trials were analyzed post hoc. Results A total of 864 patients randomized to 300 IR 5‐grass tablet or placebo were analyzed. Over the primary evaluation period, the difference in CSMS 0‐36 between the 300 IR and placebo groups was statistically significant (point estimates: −2.51, CI 95% [−3.88; −1.14], p < 0.0001 in clinical trial1; −2.31, CI 95% [−3.39; −1.23], p < 0.0001 in CT2; and −2.31, CI 95% [−3.58; −1.03], p = 0.0004 in CT3). The relative differences between the 300 IR 5‐grass tablet and placebo were −29.7%, −33.8%, and −26.3%, respectively. The results based on CSMS 0‐36 were consistent with those obtained with the primary endpoints of the trials and support the consideration of the 2‐point threshold of the CSMS 0‐36 for clinical relevance of AIT. Conclusion Post hoc analysis of 3 CTs with the 300 IR 5‐grass SLIT tablet confirmed its significant and clinically relevant effect in the European population with grass pollen‐induced ARC with or without controlled asthma.