Closed-suction drains are commonly placed after thoracolumbar surgery to reduce the risk of post-operative hematoma and neurologic deterioration, and may stay in place for a longer period of time if output remains high. Prolonged maintenance of surgical site drains, however, is associated with an increased risk of surgical site infection (SSI). The present study aims to examine the literature regarding extended duration (≥24h) prophylactic antibiotic use in patients undergoing posterior thoracolumbar surgery with closed-suction drainage. This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Relevant studies reporting the use of 24-h post-operative antibiotics compared with extended duration post-operative antibiotics in patients undergoing posterior thoracolumbar surgery with closed-suction drainage were identified from a PubMed database query. Six studies were included for statistical analysis, encompassing 1003 patients that received 24h of post-operative antibiotics and 984 patients that received ≥24h of post-operative antibiotics. The SSI rate was 5.16% for the shorter duration group (24h) and 4.44% (p=0.7865) for the longer duration group (≥24h). There is no significant difference in rates of SSI in patients receiving 24h of post-operative antibiotics compared with patients receiving ≥24h of post-operative antibiotics. Shorter durations of post-operative antibiotics in patients with thoracolumbar drains have similar outcomes compared to patients receiving longer courses of antibiotics. Shorter durations of antibiotics could potentially help lead to lower overall cost and length of stay for these patients.