INTRODUCTION Hymenoptera insect stings (ISs) in the head and neck (H&N) region are commonly considered to be a risk factor for grade IV systemic reactions (SRs) in patients with Hymenoptera venom allergy (HVA). However, clinical data addressing this issue are scarce. OBJECTIVES The aim of our study was to verify whether ISs in the H&N region were related to a higher risk of grade IV SRs in patients with HVA. PATIENTS AND METHODS This retrospective cross‑sectional study included 195 patients aged 2 to 74 years and treated with venom immunotherapy due to at least a grade II SR to ISs. The study sample comprised 109 adults (56%; mean [SD] age, 41.08 [14.62] years; male, 50.5%) and 86 children (mean [SD] age, 9.53 [4.37] years; male, 72.1%; P <0.001 for age and P = 0.002 for sex). The IS site was divided into 7 categories. RESULTS The H&N region was the most common site for the IS (one‑third of the study group). In the entire study population, the risk of grade IV SRs was numerically, though insignificantly higher for ISs in the trunk (odds ratio [OR], 1.58; 95% CI, 0.42-5.92; P = 0.50) and legs (OR, 1.56; 95% CI, 0.49-5.10; P = 0.45), as compared with the H&N region. The H&N region showed a similar risk of grade IV SRs when compared with all the other IS sites combined into a single category (OR, 0.87; 95% CI, 0.43-1.75, P = 0.7). CONCLUSIONS ISs in the H&N region were not confirmed to be a risk factor for grade IV SRs in patients with HVA, regardless of age and sex.