Introduction: Surgical site infection (SSI) is a common complication in surgery. In head and neck surgeries, different rates are reported in the indexed literature. Nowadays, this indiscriminate use of antibiotics is associated with increased cost and risks for patients. Antimicrobial misuse has also contributed to the development of antibiotic-resistant bacteria. Patients and Methods: A total of 204 patients were included in this observational retrospective cohort study. The primary outcome of this study was to describe the rate of SSI. Wound infection was considered as SSI and was defined as any cellulitis or pus drainage requiring treatment with antibiotics. Results: Of all, 127 were included in group A (not antibiotic) and 77 in group B (antibiotic prophylaxis); 109 (53.5%) patients were male, and 97 (47.5%) were female. Four (3.14%) patients developed SSI in group A and 3 (3,89%) developed SSI in group B, being not statistically significant ( P = .592). In group A, 2 patients suffered SSI after a submandibular gland resection (SGR), 1 patient after a parotid gland resection (PGR), and another one after a branchial cleft cyst resection. In group B, 1 patient suffered SSI after an SGR and 2 after a PGR. On univariate and multivariate analyses, we did not find any variable associated with the development of SSI. Conclusion: According to our results, the prophylactic antibiotic in clean, benign head and neck surgery is not necessary. Nevertheless, physicians and surgeons should be aware that severe or even fatal SSIs might be developed, and it needs to be explained to our patient before any surgery.