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Thyroid surgery is a clean procedure and therefore antibiotic prophylaxis is not routinely recommended by most international guidelines. However, antibiotics are often used in clinical practice. We enrolled 2926 patients who performed a thyroid surgical operation between the years 2009 and 2011 in the 38 centers of endocrine surgery that joined the UEC – Italian Endocrine Surgery Units Association. Antibiotic prophylaxis was used in 1132 interventions (38.7%). In case of antibiotic prophylaxis, cephalosporins or aminopenicillins ± beta lactamase inhibitors were employed. At logistic regression analysis the use of drainage or device and the presence of malignancy were independent predictors of antibiotic prophylaxis employment. In conclusion our study shows that antibiotic prophylaxis was not rarely used in clinical practice in the setting of thyroid surgery. Drainage apposition, use of device, and malignant disease were independent predictors for antibiotic prophylaxis employment. More data on everyday practice and infection rate in well-designed studies are warranted to provide definitive recommendations on the utility of antibiotic prophylaxis in this setting. According to our experience, we don’t consider to be strictly necessary the antibiotic prophylaxis employment in order to reduce infection rate in thyroid surgery.