Venous thromboembolism (VTE) continues to be a devastating source of morbidity and mortality in obese patients who suffer traumatic injuries or obese surgery patients. High incidence rates in VTE despite adherence to prevention protocols has stirred interest in new dosing regimens. The purpose of this study was to systematically review the literature and present the existing VTE chemoprophylaxis regimens for obese trauma and surgical patients in terms of efficacy and safety as measured by the incidence of VTE, anti-factor Xa levels, and the occurrence of bleeding events.An online search of seven literature databases including PubMed, Excerpta Medica Database, GoogleScholar, JAMA Network, CINAHL, Cochrane, and SAGE Journals was performed for original studies evaluating the safety and efficacy of VTE chemoprophylaxis dosing regimens according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The risk of bias was assessed using the Cochrane Risk of Bias Tool and the quality of evidence was determined using the GRADE Working Group criteria.Of the 5,083 citations identified, 45 studies with 27,717 patients met inclusion criteria. In this group, six studies evaluated weight-based dosing regimens, four employed a weight-stratified or weight-tiered strategy, five used a BMI-stratified approach, 29 assessed fixed-dose regimens, and two used continuous infusions. The majority of the studies evaluated anti-factor Xa levels as their primary outcome rather than reduction in VTE.Weight-based and high fixed-dose chemoprophylaxis regimens achieved target anti-Xa concentrations more frequently than standard fixed-dose regimens but were not associated with a reduction in VTE. Additionally, high fixed-dose approaches are associated with increased bleeding complications. Further evaluation with large randomized trials is warranted in obese trauma and obese surgical patients.Level IIIStudy Type: Systematic Review.