Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxaparin, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time. Methods A total of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r = 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU, diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant. Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin. The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities. Chin Med J 2009;122(10):1199-1202