Background: Several classifications of systemic adverse reactions (SARs) during allergen immunotherapy have been proposed, but the comparison of their usefulness in daily clinical practice is lacking. Objective: The present post hoc analysis was aimed at investigating the practicality of the most relevant international classifications proposed by the European Academy of Allergology and Clinical Immunology (EAACI), the American Academy of Asthma, Allergology and Clinical Immunology/American College of Allergy, Asthma and Immunology (AAAACI/ACAAI), and the World Allergy Organization (WAO) using data provided by the longitudinal European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI) based on daily clinical practice in 3 countries in Europe. Methods: One hundred nine SARs over 4363 allergen immunotherapy courses were classified as mild (n = 78 [71.5%]), moderate (n = 27 [24.8%]), and severe (n = 4 [3.7%]) by EASSI-doctors, which served as a criterion standard. Every SAR was further classified according to the following grading systems: EAACI 2006 Grading System (EAACI2006), WAO 2010 Grading System (WAO2010), WAO 2017 Grading System (WAO2017), and AAAAI/ACAAI Grading System. All SAR rankings were also cross-compared among each other (Kendall correlation coefficient Tau-b). In general, a low epinephrine use was identified, severe reactions occurred within 15 minutes, and milder reactions were skin only. Results: The analysis indicated disparities in mild and moderate SARs in the different grading systems. The correlation between EASSI-severity and EAACI2006, WAO2010, WAO2017, and AAAAI/ACAAI Grading System was 0.639, 0.502, 0.315, and 0.663, respectively (P < .001 in all cases). However, correlation of severe reactions was good. The best correlation with the onset of the reaction and the number of System Organ Class involved were detected in WAO grading systems. Conclusions: Despite having a lower correlation than EAACI and AAAAI/ACAAI, the WAO grading appears to provide a moderate correlation among these classifications. The analysis might help to inform clinicians and investigators on selecting the most appropriate classification.