28 studies were included in this network meta-analysis which compared efficacy and safety outcomes among thromboprophylaxis strategies and control (no treatment) following trauma of the lower extremity. Analyses were subgrouped based on site of injury, either proximal or distal to the knee. Despite some analyses demonstrating significant differences between active thromboprophylaxis strategies, primarily extended factor Xa inhibitor therapy relative to either standard low molecular weight heparin or unfractionated heparin, no significant differences in the incidence of VTE events, bleeding events, or mortality were observed for any thromboprophylaxis intervention compared to no thromboprophylaxis.