Postoperative spine surgery wound infection has been reported at up to 10.9%. Intraoperative application of vancomycin and prolonged use of postoperative prophylactic antibiotics have been used by some surgeons to decrease the rate of postoperative surgical site infection (SSI). Given the current global emphasis on rational antibiotic use, any recommendation to extend prophylaxis beyond 24 hours should be weighed against potential risks of resistance and microbiome disruption. To identify the epidemiology of postoperative spine SSI, diagnosis of infection, major risk factors contributing to infection, and current recommendation of using prophylactic systemic and local antibiotics. Literature review: 1992-2025, PubMed research words - postoperative antibiotic; Prolonged; intrawound local vancomycin, spine surgery; postoperative infection. Current recommendations for antibiotic surgical prophylaxis are: 1-2 g of cefazolin and 1-2 g of vancomycin preoperatively, dependent upon the patient’s weight and allergies. Re-dose antibiotics at 4-hour intervals during prolonged surgery. Intraoperative application of vancomycin and prolonged use of postoperative prophylactic antibiotics have been used by some surgeons to decrease the rate of postoperative SSI. There is still no current standard of care, especially in patients with high risks of postoperative wound infection. When deciding on antibiotic surgical prophylaxis, one has to consider multiple factors, including patient and surgical factors. Using local as well as prolonged postoperative systemic antibiotics may be considered in high-risk patients to decrease the rate of SSI. Recommendation to extend postoperative prophylaxis antibiotic beyond 24 hours has to be weighed against the current global emphasis on rational antibiotic use, to decrease potential risks of antibiotic resistance.