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Background: Allergies against Hymenoptera venoms are a major cause of severe anaphylaxis. Risk assessment for subjects with suspected allergy is difficult because there are currently no biomarkers that predict the likelihood of high-grade anaphylaxis other than several associated comorbidities., Objective: We investigated the relationship between the severity of anaphylaxis and the results of intracutaneous skin tests (ICTs) together with serum levels of tryptase, total IgE, and venom-specific IgE, IgG, and IgG4., Methods: We performed a retrospective evaluation of 194 patients who presented to a single medical center with allergies to bee venoms ( Apis mellifera, Bombus spp.; n=24, 12.4%), vespid venoms ( Vespula spp., Vespa spp., Polistes spp.; n=169, 87.1%), or both (n=1, 0.5%)., Results: Index bee stings occurred earlier in the year than vespid stings, although the latter were reported more frequently overall. On average, subjects who previously experienced grade IV anaphylaxis required higher dosages of venom to yield positive ICTs than those who exhibited lower grade responses. Patients diagnosed with grade IV anaphylaxis exhibited significantly lower levels of venom-specific IgE and IgG and trended toward elevated levels of tryptase. No significant differences in average levels of venom-specific IgG4 and total IgE were observed., Conclusion: Our findings reveal that intracutaneous skin testing and levels of venom-specific IgE do not predict the degree of anaphylaxis that develops in patients with venom allergy. Furthermore, the month of the index sting is not a reliable means to differentiate bee from vespid stings in patients presenting with an uncertain history., Competing Interests: Prof. Dr. Christiane Lex reports lecture fees paid to institution from Sanofi, during the conduct of the study; lecture fees paid to institution from Sanofi and Novartis, outside the submitted work. The authors report no conflicts of interest in this work., (© 2022 Hollstein et al.)