AIM: To evaluate the incidence of SSI and systemic infectious complications in a consecutive series of patients undergoing thyroid surgery in the absence of prophylactic antibiotic (NO-AP). METHODS: Prospective observational study including 77 patients who underwent total thyroidectomy and completion of previous hemithyroidectomy in NO-AP. The surgical intervention was performed by surgeons who were experienced in the procedure, and involved the use of Ligasure Harmonic Ethicon‽, absorbable hemostat in oxidized regenerated cellulose (Tabotamp‽), and skin incision suture device Skin Stapler‽. The following risk factors were assessed: gender, age, BMI, alcohol consumption, habitual smoking, co-morbidities, ASA score, indication to surgery, duration of anesthesia and procedure lenght, type of surgical procedure, fever, white blood cells count, dosage of the pre-operative C Reactive Protein in the five first post-operative day, and histological diagnosis. The data were collected and processed using IBM SPSS software v.23.0. RESULTS: No factors of increased infectious risk have been identified. No infectious surgical and systemic complications have been reported causes of prolongation of the length of the hospital stay. Conclusions: Fever, neutrophilic leukocytosis and increased PCR cannot be assessed as predictive factors of infectious complication in thyroid surgery. The cutaneous antisepsis of the operative field with chlorhexidine gluconate, the improvement of the surgical technique, the protection of the cutaneous margins of incision, the use of new devices, the accurate hemostasis and the reduction of surgery time lead to a lack of SSIs and systemic infection complications in all patients undergoing thyroid surgery in NO-AP.