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Background: The drug provocation test (DPT) and the oral food challenge (OFC) are considered as the criterion standard for the diagnosis of drug hypersensitivity reactions and food allergy. Severe allergic reactions may develop during these tests. Objective: To evaluate the frequency and features of anaphylaxis in pediatric patients undergoing OFCs and DPTs. Method: OFCs and DPTs performed in an open method in the pediatric allergy clinic of our institution between January 2014 and January 2021 were reviewed retrospectively. The characteristics of anaphylaxis that developed during these tests were evaluated. Results: A total of 3631 OFCs and/or DPTs were performed on 2588 pediatric patients. Reactions were recorded in 317 challenges (8.7%), including 42 (1.2%) in the form of anaphylaxis. Of the patients with anaphylaxis, 31 developed anaphylaxis during OFC and 11 during DPT. Anaphylaxis during OFCs was mostly triggered by yogurt (n = 8), hen's egg (n = 6), baked milk (n = 5), and baked egg (n = 4). Cases with anaphylaxis during DPT were recorded mostly with ibuprofen (54.5% [n = 6]). All patients who developed anaphylaxis during OFC had cutaneous manifestations, and 90.3% had respiratory symptoms. Gastrointestinal involvement was present in 32.3% of the patients. During DPT, cutaneous manifestations were observed in 90.9% in the patients who developed anaphylaxis and the respiratory tract was involved in 81.8%. In terms of concomitant allergic diseases, 51.6% of the patients who developed anaphylaxis during OFC had atopic dermatitis and 38.7% had asthma. All the patients with anaphylaxis triggered by nonsteroidal anti-inflammatory drug DPT had asthma. Of the anaphylaxis, 54.8% were mild, 35.7% were moderate, and 9.5% were severe. Severe anaphylaxis was recorded with baked milk (n = 2), baked egg and trimethoprim-sulfamethoxazole (n = 1, each). The patients did not require intensive care, and no death occurred. Conclusion: Anaphylaxis may develop during OFCs and DPTs. These tests should be carried out by experienced allergists in an appropriate setting where emergency equipment and medications, including epinephrine, are readily available.