Background: Multicenter studies may be required for establishing guidelines for safe usage of iodinated contrast media (ICM). Purpose: To identify the prevalence, patterns, risk factors, and preventive measures for ICM-related hypersensitivity reactions (HSRs). Materials and Methods: Between March 2017 and October 2017, a total of 196 081 patients who underwent ICM administration were enrolled from seven participating institutions. The occurrence of HSRs and baseline patient information were recorded. x2 and Student t test were performed, and logistic regression analyses were used to identify risk factors that predict occurrence and recurrence of HSR. Results: Among 196 081 patients (mean age 6 standard deviation, 59.1 years 6 16.0; 105 014 men and 91 067 women) who underwent ICM administration, the overall prevalence of HSRs was 0.73% (1433 of 196 081), and severe reactions occurred in 0.01% (17 of 196 081). Conditional logistic regression for patients with HSR (n = 1433) and a control group (1:1 matched group for age, sex, ICM product, and institution) demonstrated that a patient's previous individual history of an ICM-related HSR (adjusted odds ratio [OR], 198.8; P , .001), hyperthyroidism (adjusted OR, 3.6; P = .04), drug allergy (adjusted OR, 3.5; P , .001), and other allergic diseases (adjusted OR, 6.8; P , .001) and a family history of ICM-related HSRs (adjusted OR, 14.0; P = .01) were predictors of HSR occurrence. Logistic regression analysis showed that use of premedication with antihistamine (OR, 0.5; P = .01) and change in the generic profile of ICM (OR, 0.5; P , .001) were preventive against recurrent HSR. Conclusion: Family history as well as previous individual history of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) were risk factors for HSR occurrence, suggesting a potential genetic predisposition. A change in the culprit ICM and premedication with antihistamine are useful for reducing the recurrence of HSRs.