Evidence from 21 studies (14 Retrospective or Case Studies; 6 RCTs; 1 Review) was identified using two distinct searches to evaluate the addition of locally-delivered antibiotics to prophylactic administration of systemic antibiotics in order to further limit incidence of infection of tibial fractures fixed intramedullary nailing. The evidence presented in this systematic review and meta-analysis indicated that local antibiotics as adjunctive prophylactic therapy demonstrated lower absolute rates of infection for all tibia fracture severities. Severe fracture (GAIII) patients experienced a decrease in infection rate from 14.4% to 2.4% when local antibiotics were added. Risk of deep wound infection increased with severity of fracture, but was notably limited in patients treated with additional local antibiotics, compared to systematic antibiotics only (9% increase compared to 31% respectively with increasing severity).