Introduction: The administration of uterotonic agents during cesarean delivery is highly variable. The aim of this study was to investigate the comparison efficacy of “ Rule of Threes” algorithm with William’ s guideline in uterine tone evaluations as well as side effects of each approach in the low risk women of elective cesarean delivery (ECD). Materials and methods: This prospective and triple-blind study was conducted in 110 American Society of Anesthesiologists (ASA) physical status I– II patients with low risk of ECD. Based on administration of oxytocin the patients were randomly divided into two groups: group 1 was received oxytocin using Rule of Threes approach; group 2 was received oxytocin using William’ s guideline. In both groups total oxytocin consumption and hemodynamics changes were recorded and compared. Results: The mean dose of oxytocin was 3. 32± 0. 94 (IU)in Rule of Threes versus 6. 00± 0. 00 (IU) for William’ s group, which showed a significant difference between the two groups by independent t-test (P<0. 001). The mean total consumption of methylergonovine was 0. 003± 0. 02 (mg) for Rule of Threes group versus0. 2± 0. 02 (mg) for William’ s group which showed a significant difference between the two groups by independent t-test(P<0. 001). Out of 55 patients at 3, 6, 9, 12, and 15 min 89, 98, 98, 100 and 100 percent patients had adequate uterine tonicity in group Rule of Three, while all of the 55 patients in William’ s group had no adequate uterine tonicity at 3, 6, and 9 min as well as 96 percent of patients had adequate uterine tonicity at 12 and 15 min. No differences were observed in either groups respected to maternal hemodynamics, side effects, or blood loss. Conclusion: In both methods, no abnormal changes in hemodynamics were observed, as well as other complications associated with high doses of oxytocin. The advantages of the Rule of Threes method were high efficacy and shorter time in achieving adequate uterine tonicity, and no second-line treatment was required. Complications such as atony and abnormal bleeding were not observed during the one-day followup.