Background: Severe anaphylaxis in Hymenoptera venom allergy has been associated with a number of risk factors including elevation of baseline serum tryptase (BST), older age, concomitant diseases, and concurrent medication., Objective: The aim of this study was to evaluate indicators and risk factors for severe anaphylaxis due to Hymenoptera field stings with an emphasis on details related to the sting reaction and concurrent medication., Methods: In this single-center observational cohort study, we included 657 consecutive patients fulfilling the criteria for venom immunotherapy. Severity of sting-induced anaphylaxis was analyzed in relation to patient-specific risk factors (age and sex, preexisting cardiopulmonary conditions, cardiovascular medication) and details related to the sting reaction (culprit insect, localization of the sting, time interval to onset of symptoms, and presence or absence of cutaneous involvement). BST was determined in a subgroup of patients with moderate to severe anaphylaxis., Results: Four significant indicators and risk factors of severe anaphylaxis were identified (P < .001): (1) elevation of BST, (2) absence of urticaria or angioedema during anaphylaxis, (3) time interval of less than 5 minutes from sting to onset of symptoms, and (4) senior age. The absence of urticaria/angioedema is significantly related to BST elevation (P = .02). No relationship could be established between the severity of anaphylaxis and comorbidities or concurrent cardiovascular medication., Conclusions: Absence of urticaria/angioedema is an indicator of severe anaphylaxis and possibly mastocytosis, requiring determination of BST. Study data do not provide evidence for an aggravation of sting-induced anaphylaxis by concurrent beta-blockade or angiotensin-converting enzyme inhibition., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)