Properties of red blood cells, especially cell size and red cell indices related to size, change with time in stored blood samples. Laboratory anticoagulants have certain drawbacks. For example, heparin has no preservative property on whole blood while K 3 EDTA (EDTA) is toxic and damages platelets. The search for novel anticoagulants with better hematological profile is therefore necessary. The anticoagulant properties of aqueous leaf extract of Euphorbia heterophylla (aka ito in Igbo) were compared with those of K 3 EDTA. Specifically, the effect of this extract and K 3 EDTA on packed cell volume (PCV) and red cell indices related to size, when they were used as anticoagulants, were compared. 0.5 ml of serial dilutions of this extract were placed in specimen bottles containing 2 ml fresh human whole blood and stored for 15 days at 4°C. For control, 2 ml fresh human whole blood was added to specimen bottles containing 1.5 mg/ml EDTA and stored for 15 days at 4°C. Thereafter, the test and control samples were analyzed for PCV, MCV, MCH and MCHC using haematology autoanalyser (Erma Inc, PCE-210). All concentrations of the extract used, except 65 mg/ml, and the K 3 EDTA were able to keep the blood samples in fluid state throughout the 15 days period of storage. At the level of significance, p < 0.05, this extract had comparable preservative effect on MCV and MCH (p = 0.79; 0.20), but less preservative effect on PCV and MCHC when compared with EDTA (p = 0.013; 0.049). The aqueous leaf extract of Euphorbia heterophylla has preservative properties on haematological indices of stored human whole blood compare to that of K 3 EDTA. The fact that it does not chelate calcium as its mechanism of anticoagulation gives it an advantage over K 3 EDTA when used for biochemical tests. It should therefore, be explored as alternative laboratory anticoagulant in view of this advantage.