This study compared the effectiveness and safety of carbetocin and oxytocin in preventing postpartum hemorrhage (PPH). A systematic literature search was performed on PubMed, Embase, and the Cochrane Library for relevant studies published up to February 2019. Next, two independent reviewers screened the studies according to the selection criteria as well as the strategies recommended by the Cochrane Collaboration. Data were then extracted and evaluated. All statistical analyses were performed using RevMan 5.1. A total of 24 studies involving 37 383 patients were included for analysis. For cesarean section patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contraction (odds ratio [OR]=0.48, 95% confidence interval [CI] [0.35, 0.65], p < 0.00001), PPH (OR=0.70, 95% CI [0.51, 0.95], p=0.02), blood loss (mean [MD]=-64.36, 95% CI [-107.78, -20.93], p=0.004), and transfusion (OR=0.59, 95% CI [0.42, 0.82], p=0.002), and there was no significant difference in severe PPH (OR=0.84, 95% CI [0.66, 1.090], p=0.19). For vaginal delivery patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contractions (OR=0.48, 95% CI [0.25, 0.93], p=0.03), PPH (OR=0.28, 95% CI [0.09, 0.91], p=0.03), and blood loss (MD=-63.52, 95% CI [-113.43, -13.60], p=0.01), and there were no significant differences in severe PPH (OR=0.82, 95% CI [0.40, 1.69], p=0.59) and transfusion (OR=0.60, 95% CI [0.22, 1.61], p=0.31). With regard to safety, for cesarean section patients, carbetocin was superior to oxytocin in reduction of the incidence of headache (OR=0.72, [0.55, 0.95], p=0.02), and there were no significant differences in nausea, vomiting, abdominal pain, flushing, tremors, itching, dizziness, and fever. For vaginal delivery patients, there were no significant differences in nausea, vomiting, headache, abdominal pain, flushing, tremors, itching, dizziness, and fever between the two drugs. For patients undergoing cesarean section and vaginal delivery, carbetocin was superior to oxytocin in effectiveness and similar in safety. Therefore, carbetocin is expected to be an alternative uterine contraction agent for preventing PPH.