OBJECTIVE：To observe the success rate and safety of diphenhydramine combined with prednisone in the prevention of iodine-containing contrast agent allergic reactions. METHODS： 1 day before surgery， 42 patients with positive iodine allergy test was given 40 mg Prednisone tablet， orally， 3 times a day， 50 mg diphenhydramine was given by intramuscular injection and 1 ml iodine contrast by intravenous injection （allergy test performed again）1 h before surgery. After all patients used iodine contrast in 15 min， vascular interventional treatment was conducted if there was no bronchospasm， angioedema， leather ball sample itchy rash， hypotension， itching and other allergic reactions. Prevention success rate were observed， and the incidence of adverse reactions was recorded. RESULTS： Prevention success rate was 90.48％， the incidence of adverse reactions was 7.14％， and it self-improved after stopping drugs. CONCLUSIONS： Diphenhydramine combined with prednisone has high success rate in the prevention of iodine-containing contrast agent allergic reactions， with good safety.