Objective: To quantify anesthesia-related complications associated with cesarean delivery in a well-described, prospectively ascertained cohort from multiple university-based hospitals in the United States and to evaluate whether certain factors would identify women at increased risk for a failed regional anesthetic. Methods: A prospective observational study was conducted of women (n = 37,142) with singleton gestations undergoing cesarean delivery in the centers forming the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Detailed information was collected regarding choice of anesthesia and procedure-related complications, including failed regional anesthetic and maternal death. Potential risk factors for a failed regional anesthetic were analyzed. Results: Of the women studied, 34,615 (93% ) received a regional anesthetic. Few (3.0% ) regional procedures failed, and related maternal morbidity was rare. Increased maternal size, higher preoperative risk, rapid decision-to-incision interval, and placement later in labor were all significantly related to an increased risk of a failed regional procedure. Of the general anesthetics, 38% were administered when the decision-to-incision interval was less than 15 minutes. Women deemed at the greatest preoperative risk (American Society of Anesthesiologists score ≥ 4) were approximately 7-fold more likely to receive a general anesthetic (odds ratio 6.9, 95% confidence interval 5.83-8.07). There was one maternal death, due to a failed intubation, in which the anesthetic procedure was directly implicated. Conclusion: Regional techniques have become the preferred method of anesthesia for cesarean delivery. Procedure-related complications are rare and attest to the safety of modern obstetric anesthesia for cesarean delivery in the United States. Objective: To quantify anesthesia-related complications associated with cesarean delivery in a well-described, prospectively ascertained cohort from multiple university-based hospitals in the United States and to evaluate whether certain factors would identify women at increased risk for a failed regional anesthetic. Methods : A prospective observational study conducted of women (n = 37,142) with singleton gestations undergoing cesarean delivery in the centers forming the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Detailed information was was taken versus choice of anesthesia and procedure -related complications, including failed regional anesthetic and maternal death. Potential risk factors for a failed regional anesthetic were analyzed. Results: Of the women studied, 34,615 (93%) received a regional anesthetic. Few (3.0%) regional procedures failed, and related maternal morbidity was rare. Increased maternal size, higher pre operative risk, rapid decision-to-incision interval, and placement later in labor were all significantly related to an increased risk of a failed regional procedure. Of the general anesthetics, 38% were administered when the decision-to-incision interval was less than 15 minutes. Women deemed at the greatest preoperative risk (American Society of Anesthesiologists score ≥ 4) were approximately 7-fold more likely to receive a general anesthetic (odds ratio 6.9, 95% confidence interval 5.83-8.07). There was one maternal death , due to a failed intubation, in which the anesthetic procedure was directly implicated. Conclusion: Regional techniques have become the preferred method of anesthesia for cesarean delivery. Procedure-related complications are rare and attest to the safety of modern obstetric anesthesia for cesarean delivery in the United States.