The objective of this systematic review was to estimate the efficacy and safety of high-dose vs low-dose oxytocin for labor augmentation on the risk of cesarean section and on indicators of maternal and neonatal morbidity. We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for randomized clinical trials published until January 2010. Ten randomized clinical trials, including 5423 women, met the inclusion criteria. High-dose oxytocin was associated with a moderate decrease in the risk of cesarean section (relative risk RR, 0.85; 95% confidence interval CI, 0.75–0.97), a small increase in spontaneous vaginal delivery (RR, 1.07; 95% CI, 1.02–1.12), and a decrease in labor duration (mean difference: –1.54 hours, 95% CI, –2.44 to –0.64). While hyperstimulation was increased with high-dose oxytocin (RR, 1.91; 95% CI, 1.49–2.45), there was no evidence of an increase in maternal or neonatal morbidity. We conclude that high-dose oxytocin for labor augmentation is associated with a decrease in cesarean section and shortened labor.