The Affiliated Hospital of Yunnan University, serving as the Poisoning Treatment Center of Yunnan Province, receives nearly all patients with wild mushroom poisoning requiring emergency treatment. We anecdotally observed a higher incidence of anaphylactoid reactions in patients admitted to our hospital for wild mushroom poisoning who received acetylcysteine. This retrospective cohort study was conducted from January 1, 2023, to August 31, 2024. The study included patients who received intravenous acetylcysteine. Patients were divided into two groups: the exposure group comprised patients with wild mushroom poisoning, while the comparison group included patients receiving acetylcysteine for other indications. The primary outcome measure was the occurrence of anaphylactoid reactions. Subgroup analyses were performed for sex, age, weight, dose, history of allergies, total bilirubin concentration, alanine aminotransferase activity, aspartate aminotransferase activity, gamma-glutamyl transferase activity, alkaline phosphatase activity, prothrombin time, and the fastest rate of acetylcysteine infusion. One-hundred and ten patients were included: 20 with wild mushroom poisoning and 90 without. Patients with wild mushroom poisoning exhibited a significantly higher risk of anaphylactoid reactions (OR: 5.43; 95% CI: 1.63-18.13). Symptoms of anaphylactoid reactions were typically mild. Additionally, female gender (OR: 3.49; 95% CI: 1.02-11.95) and history of allergies (OR: 3.82; 95% CI: 1.11-13.20) were identified as independent risk factors. A predictive model combining these factors showed good performance (area under the receiver operating characteristic curve 0.88; 95% CI: 0.81-0.95). A possible reason for this phenomenon is the presence of various trace mineral elements in wild mushrooms, which exhibit higher bioavailability when mushrooms are not cooked fully. Accumulated mineral elements in wild mushroom poisoning patients bind with acetylcysteine, forming substances that cause anaphylactoid reactions. Patients with wild mushroom poisoning appear to be at an increased risk of anaphylactoid reactions during intravenous acetylcysteine administration compared to those who did not consume wild mushrooms.