Currently several generic versions of a branded low molecular weight heparin (LMWH; enoxaparin, Sanofi-Aventis, Paris, France) have become available for clinical use in several countries. Such products include Cutenox (Gland Pharma, Hyderabad, India), Dripanina (Ariston, São Paulo, Brazil) and Clenox (Pharmayect, Barranquilla, Columbia). Although these products are not currently approved for use in the U.S., several other manufacturers have sought FDA approval for their products. Due to a lack of specifications and guidelines, this approval is still pending. In order to compare the relative potency of different anti-factor Xa U/ml adjusted generic preparations, studies were designed to compare each of the individual generic LMWHs with the branded product. Additionally, multiple batches of some of the generic products were also profiled. All of the agents were tested in human whole blood and citrated plasma over a concentration range of 0.15 to 10 U/ml. Whole blood activated clotting time (ACT) and thrombelastography (TEG) measurements along with fibrinopeptide A (FPA) generation were compared. The plasmatic tests included anti-Xa and anti-IIa activity by amidolytic assay and aPTT, Heptest and PiCT clotting time assays. In addition, protamine sulfate neutralization profiles for these agents were investigated at fixed protamine concentrations of 12.5 and 25 μg/ml. In the whole blood assays, at concentrations < 2.5 U/ml, no significant differences were observed between the branded and potency adjusted generic LMWHs. However, in the plasma-based systems, assay-dependent variations were observed which were more obvious at concentrations > 1.25 U/ml (aPTT, anti-IIa, anti-Xa; p<0.05). Similarly, product and assay based variations were also observed in the protamine neutralization profile of these LMWHs. Moreover, marked differences in some assays were observed when different batches of the generic copies of LMWHs were tested. Additional studies carried out to profile the oligosaccharide composition also showed product and batch-dependent variations. The relative amounts of antithrombin affinity components among the different generic products and within product batches also exhibited some variations. These studies clearly demonstrate that some of the generic copies of enoxaparin may not produce comparable anticoagulant and thrombin generation inhibitory effects at anti-Xa potency adjusted doses. Such differences may not be clinically relevant in the prophylactic indications (dosages ≤ 40 mg O.D). However, in therapeutic or interventional indications (IV or SC dosage > 100 mg), these products may exhibit differential safety/efficacy profiles. These observations underscore the importance of clear guidelines on the chemical and biologic specifications for the acceptance of generic versions of LMWHs. Such measures are crucial to avoid any potential safety/inefficacy issues particulatly in indications where these drugs are used at higher dosages.