To determine the effect of anti-factor Xa assay dosing of low-molecular-weight heparin (LMWH) on rates of venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, and mortality among orthopaedic trauma patients. PubMed/MEDLINE, Embase, Ovid, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov , and Scopus were systematically searched from inception of the database to 2021. Prospective, retrospective, and randomized controlled trial studies were included if they compared rates of VTE, DVT, PE, bleeding, and/or mortality between orthopaedic trauma patients receiving anti-factor Xa-based LMWH dosing and those receiving standard dosing. Two independent reviewers screened titles and abstracts for eligibility. Study characteristics including study design, inclusion criteria, and intervention were extracted. Meta-analysis was performed using pooled proportion of events (effect size) with 95% confidence intervals. A random-effects model was used. Heterogeneity was quantified by Higgins I 2 . Heterogeneity and variability between subgroups indicated differences in the pooled estimate represented by a P -value. Six hundred eighty-five studies were identified, and 10 studies including 2870 patients were included. In total, 30.3% and 69.7% received an adjusted and nonadjusted dose of LMWH, respectively. The rate of VTE and DVT were significantly lower in the anti-factor Xa-adjusted cohort, whereas there was no statistically significant difference in rates of PE, bleeding, or mortality between the cohorts. This systematic review and meta-analysis demonstrates that anti-factor Xa activity assay dosing of LMWH among orthopaedic trauma patients leads to a reduction in overall DVT rates, although not PE rates, without an increased risk of bleeding events. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.