Six randomized controlled trials including 407 patients with open tibial fractures were included in this systematic review and meta-analysis comparing external fixation (EF) versus unreamed tibial intramedullary nailing (UTN). Pooled outcomes of interest included postoperative superficial and deep infections, malunion, delayed union, nonunion, and hardware failure. UTN significantly reduced the rates of superficial infection and malunion compared to EF, while both treatments showed similar effectiveness for deep infections, delayed union, and nonunion. EF, however, resulted in fewer hardware failures. This analysis suggests that UTN might be preferred for managing open tibial fractures, with careful monitoring of postoperative weight-bearing to prevent hardware failure.