OBJECTIVE To estimate the efficacy of the routine use of intraumbilical vein injection of oxytocin with active management of the third stage of labor in reducing blood loss and length of the third stage. METHODS In this prospective, randomized, double-blind trial, 412 women undergoing vaginal delivery who did not have risk factors for postpartum hemorrhage were randomly allocated to receive either 20 international units oxytocin diluted with 26 mL saline (n=207) or 30 mL saline (n=205) by intraumbilical vein injection. Active management of the third stage of labor (prophylactic injection of 10 international units oxytocin within 2 minutes of birth, early clamping of the umbilical cord, and controlled cord traction) was used in both groups. The primary outcome was mean blood loss during the third and fourth stages of labor. RESULTS The mean estimated blood loss was significantly lower in women treated with oxytocin compared with women in the placebo group (195.3+/-81.0 mL compared with 288.3+/-134.1 mL, respectively; P<.001). The third stage of labor was significantly shorter in the oxytocin group than in the placebo group (4.5+/-1.6 minutes compared with 7.9+/-3.4 minutes, respectively; P<.001). The percentages of placentas remaining undelivered beyond 15 minutes were 0% in the oxytocin group and 4.4% in the placebo group (P=.002). CONCLUSIONS The use of intraumbilical injection of oxytocin with the active management of the third stage of labor significantly reduced postpartum blood loss and the duration of the third stage. BACKGROUND ClinicalTrials.gov, www.clinicaltrials.gov, NCT01094028. METHODS I.