Hip replacement surgery carries a high risk of thromboembolic complications, and pharmacological prophylaxis is routinely adopted in clinical practice. Meta-analyses have indicated that low molecular weight heparins (LMWHs) are clinically superior to conventional prophylaxis with unfractionated heparin. These analyses have regarded LMWHs as one chemical entity, despite differences in their physicochemical, biological, and pharmacodynamic properties. Comparing data from trials of different LMWHs is difficult despite standardization in trial design, patient selection criteria, and efficacy assessments, as the influences of concurrent disease and variation in venogram interpretation are difficult to interpret. Furthermore, variations in bleeding assessment limit conclusions on the safety profile of different LMWHs. Two clinical trials have compared enoxaparin with tinzaparin and reviparin respectively. Efficacy equivalence was demonstrated despite differences in the anti-Xa activities of the doses given. These trials support the position of the United States Food and Drug Administration and the World Health Organization that LMWHs are distinct, noninterchangeable compounds and cannot be therapeutically substituted based upon anti-factor Xa levels. The extent of clinical experience with each LMWH is an important factor influencing clinical use.