Subcutaneous heparin administration is routinely used for many patients in orthopaedic clinics. Nurses frequently encounter ecchymosis formation with heparin administration. Previous research indicates that the administration protocol may have effect on ecchymosis formation. The study was performed to determine and compare the effect of three different approaches of subcutaneous enoxaparin injection on ecchymosis formation in patients who underwent joint replacement surgery. Three protocols were compared: (1) injecting enoxaparin in 10 seconds, (2) injecting enoxaparin in 30 seconds, and (3) injecting enoxaparin in 30 seconds and waiting for an additional 10 seconds before withdrawing the needle. Ecchymosis formation was assessed in both size and frequency. Descriptive statistics, Kruskal-Wallis analysis, Mann-Whitney U test, and Spearman rank correlation test were used to assess the data. The ecchymosis frequency was higher in the 10-second administration. Ecchymosis size was smaller when the enoxaparin was administered in 30 seconds and the needle was kept in the tissue for 10 seconds after injection. The enoxaparin should be administered in a longer duration (30 seconds). Keeping the needle in the tissue for 10 seconds may further decrease the size but not the incidence of ecchymosis.