Antibiotic prophylaxis following delayed sternal closure in pediatric cardiac surgery is not standardized. We systematically reviewed relevant literature published between 1990 and 2019 to aid future trial design. Patient characteristics, antimicrobial prophylaxis regimens, and postoperative incidence of infection were collected. Twenty-eight studies described 36 different regimens in over 3,000 patients. There were 11 single-drug regimens and 25 multidrug regimens. Cefazolin-only was the most common regimen (9/36, 25%). The overall incidence of surgical site infection was 7.5% (217/2,910 patients) and bloodstream infection was 7.4% (123/1,667 patients). In the 2010s, multidrug regimens were associated with a significantly lower incidence of both surgical site infections (4.6% vs. 20%, P < .001) and bloodstream infections (6.0% vs. 50%, P < .001) compared to single-drug regimens.